Method of making a stent

ABSTRACT

A method of manufacturing a stent is disclosed. The stent includes a minimum crimped diameter such that in the minimum crimped diameter, a pair of stent rings, between which marker support structures reside, do not make contact with the marker support structures. The crimped profile of the stent of the present invention can be as small as the crimped profile of a same stent but without the marker support structures.

PRIORITY CLAIM

This application is a continuation of application Ser. No. 14/097,172,filed on Dec. 4, 2013, which in turn is a continuation of applicationSer. No. 14/042,512, filed on Sep. 30, 2013, which is a continuation ofapplication Ser. No. 13/015,488 (U.S. Pat. No. 8,568,471), filed on Jan.27, 2011, which claimed the benefit of U.S. provisional application No.61/385,891, filed on Sep. 23, 2010, U.S. provisional application No.61/385,902, filed Sep. 23, 2010, and U.S. provisional application No.61/299,968, filed on Jan. 30, 2010. Application Ser. Nos. 14/097,172,14/042,512, and 13/015,488 and provisional applications 61/385,891,61/385,902 and 61/299,968 are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to drug-eluting medical devices; moreparticularly, this invention relates to polymeric scaffolds that areexpanded by a delivery balloon.

BACKGROUND OF THE INVENTION

Radially expandable endoprostheses are artificial devices adapted to beimplanted in an anatomical lumen. An “anatomical lumen” refers to acavity, duct, of a tubular organ such as a blood vessel, urinary tract,and bile duct. Stents are examples of endoprostheses that are generallycylindrical in shape and function to hold open and sometimes expand asegment of an anatomical lumen (one example of a stent is found in U.S.Pat. No. 6,066,167 to Lau et al). Stents are often used in the treatmentof atherosclerotic stenosis in blood vessels. “Stenosis” refers to anarrowing or constriction of the diameter of a bodily passage ororifice. In such treatments, stents reinforce the walls of the bloodvessel and prevent restenosis following angioplasty in the vascularsystem. “Restenosis” refers to the reoccurrence of stenosis in a bloodvessel or heart valve after it has been treated (as by balloonangioplasty, stenting, or valvuloplasty) with apparent success.

The treatment of a diseased site or lesion with a stent involves bothdelivery and deployment of the stent. “Delivery” refers to introducingand transporting the stent through an anatomical lumen to a desiredtreatment site, such as a lesion. “Deployment” corresponds to expansionof the stent within the lumen at the treatment region. Delivery anddeployment of a stent are accomplished by positioning the stent aboutone end of a catheter, inserting the end of the catheter through theskin into an anatomical lumen, advancing the catheter in the anatomicallumen to a desired treatment location, expanding the stent at thetreatment location, and removing the catheter from the lumen.

In the case of a balloon expandable stent, the stent is mounted about aballoon disposed on the catheter. Mounting the stent typically involvescompressing or crimping the stent onto the balloon prior to insertion inan anatomical lumen. At the treatment site within the lumen, the stentis expanded by inflating the balloon. The balloon may then be deflatedand the catheter withdrawn from the stent and the lumen, leaving thestent at the treatment site. In the case of a self-expanding stent, thestent may be secured to the catheter via a retractable sheath. When thestent is at the treatment site, the sheath may be withdrawn which allowsthe stent to self-expand.

The stent must be able to satisfy a number of basic, functionalrequirements. The stent must be capable of withstanding the structuralloads, for example, radial compressive forces, imposed on the stent asit supports the walls of a vessel after deployment. Therefore, a stentmust possess adequate radial strength. After deployment, the stent mustadequately maintain its size and shape throughout its service lifedespite the various forces that may come to bear on it. In particular,the stent must adequately maintain a vessel at a prescribed diameter fora desired treatment time despite these forces. The treatment time maycorrespond to the time required for the vessel walls to remodel, afterwhich the stent is no longer necessary for the vessel to maintain adesired diameter.

Radial strength, which is the ability of a stent to resist radialcompressive forces, relates to a stent's radial yield strength andradial stiffness around a circumferential direction of the stent. Astent's “radial yield strength” or “radial strength” (for purposes ofthis application) may be understood as the compressive loading, which ifexceeded, creates a yield stress condition resulting in the stentdiameter not returning to its unloaded diameter, i.e., there isirrecoverable deformation of the stent. When the radial yield strengthis exceeded the stent is expected to yield more severely and only aminimal force is required to cause major deformation.

Even before the radial yield strength is exceeded there may be permanentdeformation in the stent a following radial compressive load, but thisdegree of permanent deformation somewhere in the stent is not severeenough to have a significant effect on the stent's overall ability toradially support a vessel. Therefore, in some cases the art may view“radial yield strength” as the maximum radial loading, beyond which thescaffold stiffness changes dramatically. “Radial yield strength” unitsare sometimes force-divided-by-length, which is an expression of radialyield strength on a per-unit-length basis. Thus, for a radial yieldstrength per unit length, e.g., F N/mm, the radial load which, if itexceeds this value, would result in significant change in stiffness fora stent having two different lengths, L1 and L2, would therefore be theproduct F*L1 and F*L2, respectively. The value F, however, is the samein both cases, so that a convenient expression can be used to appreciatethe radial yield strength independent of the length of the stent.Typically, the radial force that identifies the point where stiffness islost does not change much on a per-unit-length basis when the stentlength changes.

Stents implanted in coronary arteries are primarily subjected to radialloads, typically cyclic in nature, which are due to the periodiccontraction and expansion of vessels as blood is pumped to and from abeating heart. Stents implanted in peripheral blood vessels, or bloodvessels outside the coronary arteries, e.g., iliac, femoral, popliteal,renal and subclavian arteries, however, must be capable of sustainingboth radial forces and crushing or pinching loads. These stent types areimplanted in vessels that are closer to the surface of the body. Becausethese stents are close to the surface of the body, they are particularlyvulnerable to crushing or pinching loads, which can partially orcompletely collapse the stent and thereby block fluid flow in thevessel.

As compared to a coronary stent, which is limited to radial loads, aperipheral stent must take into account the significant differencesbetween pinching or crushing loads and radial loads, as documented inDuerig, Tolomeo, Wholey, Overview of superelastic stent Design, MinInvas Ther & Allied Technol 9(3/4), pp. 235-246 (2000) and Stoeckel,Pelton, Duerig, Self-Expanding Nitinol Stents—Material and DesignConsiderations, European Radiology (2003). The corresponding crushingand radial stiffness properties of the stent also can vary dramatically.As such, a stent that possesses a certain degree of radial stiffnessdoes not, generally speaking, also indicate the degree of pinchingstiffness possessed by the stent. The two stiffness properties are notthe same, or even similar.

The amount of cross-sectional crush expected for a peripheral stentimplanted within the femoral artery has been estimated to be about5.8+/−7%, 6.5+/−4.9% and 5.1+/−6.4% at the top, middle and bottomportions of the femoral artery in older patients and 2.5+/−7.7%,−0.8+/−9.4% and −1.5+/−10.5% for younger patients. Other considerationsfor peripheral stents are the degree of bending and axial compressionthe stent can withstand without mechanical loss of strength/stiffness.As compared to coronary stents, a peripheral stent usually has lengthsof between about 36 and 40 mm when implanted in the superficial femoralartery, as an example. As such, the stent must be flexible enough towithstand axial compression and bending loading without failure. Theamount of bending and axial compression expected has been studied andreported in Nikanorov, Alexander, M. D. et al., Assessment ofself-expanding Nitinol stent deformation after chronic implantation intothe superficial femoral artery.

To date the most commonly used type of peripheral stent areself-expanding stents made from super-elastic material, such as Nitinol.This type of material is known for its ability to return to its originalconfiguration after severe deformation, such as a crushing load orlongitudinal bending. However, this variety of self-expanding stentshave undesired qualities; most notably, the high resiliency ofsuper-elastic material produces what is commonly referred to as a“chronic outward force” (COF) on the blood vessel supported by thestent. Complications resulting from COF are discussed in Schwartz, LewisB. et al. Does Stent Placement have a learning curve: what mistakes dowe as operators have to make and how can they be avoided?, AbbottLaboratories; Abbott Park, Ill., USA. It is believed that a COF exertedon a blood vessel by a self-expending stent is a main contributor tohigh degrees of restenosis of lesions treated by the self-expandingstent. It has been shown that not even an anti-proliferative drugdelivered from drug eluting self-expandable stents can mitigate therestenosis caused by the stent's COF.

Stents that are plastically deformed by a balloon to support a vessel donot suffer from this drawback. Indeed, balloon expanded stents, incontrast to self-expanding stents made from a super-elastic material,have the desirable quality of being deployable to the desired diameterfor supporting the vessel without exerting residual outward forces onthe vessel. However, the prior art has concluded that plasticallydeformed stents, once collapsed, pinched or crushed in a peripheralartery will remain so, permanently blocking the vessel. The prior arthas concluded, therefore, that plastically deformed stents pose anundesirable condition to the patient and should not be used to treatperipheral blood vessels.

A polymer scaffold, such as that described in US 2010/0004735 is madefrom a biodegradable, bioabsorbable, bioresorbable, or bioerodablepolymer. The terms biodegradable, bioabsorbable, bioresorbable,biosoluble or bioerodable refer to the property of a material or stentto degrade, absorb, resorb, or erode away from an implant site. Thepolymer scaffold described in US 2010/0004735, as opposed to a metalstent, is intended to remain in the body for only a limited period oftime. The scaffold is made from a biodegradable or bioerodable polymer.In many treatment applications, the presence of a stent in a body may benecessary for a limited period of time until its intended function of,for example, maintaining vascular patency and/or drug delivery isaccomplished. Moreover, it is believed that biodegradable scaffoldsallow for improved healing of the anatomical lumen as compared to metalstents, which may lead to a reduced incidence of late stage thrombosis.In these cases, there is a desire to treat a vessel using a polymerscaffold, in particular a bioerodible polymer scaffold, as opposed to ametal stent, so that the prosthesis's presence in the vessel is for alimited duration. However, there are numerous challenges to overcomewhen developing a polymer scaffold.

The art recognizes a variety of factors that affect a polymericscaffold's ability to retain its structural integrity and/or shape whensubjected to external loadings, such as crimping and balloon expansionforces. These interactions are complex and the mechanisms of action notfully understood. According to the art, characteristics differentiatinga polymeric, bio-absorbable scaffold of the type expanded to a deployedstate by plastic deformation from a similarly functioning metal scaffoldare many and significant. Indeed, several of the accepted analytic orempirical methods/models used to predict the behavior of metallicscaffolds tend to be unreliable, if not inappropriate, as methods/modelsfor reliably and consistently predicting the highly non-linear, timedependent behavior of a polymeric load-bearing structure of aballoon-expandable scaffold. The models are not generally capable ofproviding an acceptable degree of certainty required for purposes ofimplanting the scaffold within a body, or predicting/anticipating theempirical data.

Moreover, it is recognized that the state of the art in medicaldevice-related balloon fabrication, e.g., non-compliant balloons forscaffold deployment and/or angioplasty, provide only limited informationabout how a polymeric material might behave when used to support a lumenwithin a living being via plastic deformation of a network of ringsinterconnected by struts. In short, methods devised to improvemechanical features of an inflated, thin-walled balloon structure, mostanalogous to mechanical properties of a pre-loaded membrane when theballoon is inflated and supporting a lumen, simply provides little, ifany insight into the behavior of a deployed polymeric scaffold. Onedifference, for example, is the propensity for fracture or cracks todevelop in a polymer scaffold. The art recognizes the mechanical problemas too different to provide helpful insights, therefore, despite ashared similarity in class of material. At best, the balloon fabricationart provides only general guidance for one seeking to improvecharacteristics of a balloon-expanded, bio-absorbable polymericscaffold.

Polymer material considered for use as a polymeric scaffold, e.g.poly(L-lactide) (“PLLA”), poly(L-lactide-co-glycolide) (“PLGA”),poly(D-lactide-co-glycolide) or poly(L-lactide-co-D-lactide)(“PLLA-co-PDLA”) with less than 10% D-lactide, and PLLD/PDLA stereocomplex, may be described, through comparison with a metallic materialused to form a stent, in some of the following ways. A suitable polymerhas a low strength to weight ratio, which means more material is neededto provide an equivalent mechanical property to that of a metal.Therefore, struts must be made thicker and wider to have the requiredstrength for a stent to support lumen walls at a desired radius. Thescaffold made from such polymers also tends to be brittle or havelimited fracture toughness. The anisotropic and rate-dependant inelasticproperties (i.e., strength/stiffness of the material varies dependingupon the rate at which the material is deformed) inherent in thematerial, only compound this complexity in working with a polymer,particularly, bio-absorbable polymer such as PLLA or PLGA.

Processing steps performed on, and design changes made to a metal stentthat have not typically raised concerns for, or required carefulattention to unanticipated changes in the average mechanical propertiesof the material, therefore, may not also apply to a polymer scaffold dueto the non-linear and sometimes unpredictable nature of the mechanicalproperties of the polymer under a similar loading condition. It issometimes the case that one needs to undertake extensive validationbefore it even becomes possible to predict more generally whether aparticular condition is due to one factor or another—e.g., was a defectthe result of one or more steps of a fabrication process, or one or moresteps in a process that takes place after scaffold fabrication, e.g.,crimping? As a consequence, a change to a fabrication process,post-fabrication process or even relatively minor changes to a scaffoldpattern design must, generally speaking, be investigated more thoroughlythan if a metallic material were used instead of the polymer. Itfollows, therefore, that when choosing among different polymericscaffold designs for improvement thereof, there are far less inferences,theories, or systematic methods of discovery available, as a tool forsteering one clear of unproductive paths, and towards more productivepaths for improvement, than when making changes in a metal stent.

The present inventors recognize, therefore, that, whereas inferencespreviously accepted in the art for stent validation or feasibility whenan isotropic and ductile metallic material was used, those inferenceswould be inappropriate for a polymeric scaffold. A change in a polymericscaffold pattern may affect not only the stiffness or lumen coverage ofthe scaffold in its deployed state supporting a lumen, but also thepropensity for fractures to develop when the scaffold is crimped orbeing deployed. This means that, in comparison to a metallic stent,there is generally no assumption that can be made as to whether achanged scaffold pattern may not produce an adverse outcome, or requirea significant change in a processing step (e.g., tube forming, lasercutting, crimping, etc.). Simply put, the highly favorable, inherentproperties of a metal (generally invariant stress/strain properties withrespect to the rate of deformation or the direction of loading, and thematerial's ductile nature), which simplify the stent fabricationprocess, allow for inferences to be more easily drawn between a changedstent pattern and/or a processing step and the ability for the stent tobe reliably manufactured with the new pattern and without defects whenimplanted within a living being.

A change in the pattern of the struts and rings of a polymeric scaffoldthat is plastically deformed, both when crimped to, and when laterdeployed by a balloon, unfortunately, is not predictable to the same orsimilar degree as for a metal stent. Indeed, it is recognized thatunexpected problems may arise in polymer scaffold fabrication steps as aresult of a changed pattern that would not have necessitated any changesif the pattern was instead formed from a metal tube. In contrast tochanges in a metallic stent pattern, a change in polymer scaffoldpattern may necessitate other modifications in fabrication steps orpost-fabrication processing, such as crimping and sterilization.

In addition to meeting the requirements described above, it is desirablefor a scaffold to be radiopaque, or fluoroscopically visible underx-rays. Accurate placement is facilitated by real time visualization ofthe delivery of a scaffold. A cardiologist or interventional radiologistcan track the delivery catheter through the patient's vasculature andprecisely place the scaffold at the site of a lesion. This is typicallyaccomplished by fluoroscopy or similar x-ray visualization procedures.For a scaffold to be fluoroscopically visible it must be more absorptiveof x-rays than the surrounding tissue. Radiopaque materials in ascaffold may allow for its direct visualization. However, a significantshortcoming of a biodegradable polymer scaffold (and polymers generallycomposed of carbon, hydrogen, oxygen, and nitrogen) is that they areradiolucent with no radiopacity. Biodegradable polymers tend to havex-ray absorption similar to body tissue. One way of addressing thisproblem is to attach radiopaque markers to structural elements of thestent. A radiopaque marker can be disposed within a structural elementin such a way that the marker is secured to the structural element.However, the use of stent markers on polymeric stents entails a numberof challenges. One challenge relates to the difficulty of insertion ofmarkers. These and related difficulties are discussed in US2007/0156230.

There is a need to develop a prosthesis for treating peripheral bloodvessels that possesses the desirable qualities of a balloon expandedstent, which does not exert residual outward forces on the vessel (as inthe case of a self-expanding stent) while, at the same time, beingsufficiently resilient to recover from a pinching or crushing load in aperipheral blood vessel, in addition to the other loading eventsexpected within a peripheral blood vessel that are not typicallyexperienced by a coronary scaffold. There is also a need to fabricatesuch a polymer scaffold so that the prosthesis also is capable ofpossessing at least a minimum radial strength and stiffness required tosupport a peripheral blood vessel; a low crossing profile; and a limitedpresence in the blood vessel. There is also a need for a scaffold thatis easily monitored during its pendency using standard imagingtechniques, and is capable of high yield production.

SUMMARY OF THE INVENTION

The invention provides a polymer scaffold suited to address theforegoing needs including high crush recoverability, e.g., at leastabout 90-95% after a 50% crushing load. The scaffold is cut from apolymer tube and crimped to a balloon. Accordingly, the inventionprovides a balloon expandable, plastically deformed scaffold cut from atube and being suitable for use as a peripheral scaffold. As such, thedrawbacks of self-expanding stents can be obviated by practicing theinvention.

To date the art has relied on metals or alloys for support and treatmentof peripheral blood vessels. As mentioned earlier, once a metallic stentis implanted it remains in the body permanently, which is not desired. Ascaffold made from a material that dissolves after it treats an occludedvessel, therefore, would be preferred over a metal stent. A polymer,however, is much softer than a metal. If it will serve as a replacementto metal, a new design approach is needed.

High radial force, small crimped profile and crush recovery is needed inthe polymer scaffold. If the material cannot be modified enough to meetthese needs, then a modification to the design of the scaffold networkof struts is required. There are a few known approaches to increase theradial yield strength. One is to increase the wall thickness and anotheris to increase the strut width. Both of these modifications, however,will result in greater profile of the device at the crimped state. Asmall crimped profile of the device and increased stiffness and strengthis therefore necessary and heretofore not addressed in the art.

As will be appreciated, aspects of a polymer scaffold disclosed hereincontradict conclusions that have been previously made in the artconcerning the suitability of a balloon-expandable stent, or scaffoldfor use in peripheral blood vessels. The problems concerningself-expanding stents are known. Therefore a replacement is sought.However, the conventional wisdom is that a balloon expanded stent havingsufficient radial strength and stiffness, as opposed to a self-expandingstent, is not a suitable replacement, especially in vessels that willimpose high bending and/or crushing forces on the implanted prosthesis.

According to the invention, crush-recoverable polymer scaffoldspossessing a desired radial stiffness and strength, fracture toughnessand capability of being crimped down to a target delivery diameter willproperly balance three competing design attributes: radialstrength/stiffness verses toughness, in-vivo performance versescompactness for delivery to a vessel site, and crush recovery versesradial strength/stiffness.

Disclosed herein are embodiments of a scaffold that can effectivelybalance these competing needs, thereby providing an alternative toprostheses that suffer from chronic outward force. As will beappreciated from the disclosure, various polymer scaffold combinationswere fabricated and tested in order to better understand thecharacteristics of a scaffold that might address at least the followingneeds:

Crush recoverability of the scaffold without sacrificing a desiredminimal radial stiffness and strength, recoil, deploy-ability andcrimping profile;

Acute recoil at deployment—the amount of diameter reduction within ½hour of deployment by the balloon;

Delivery/deployed profile—i.e., the amount the scaffold could be reducedin size during crimping while maintaining structural integrity;

In vitro radial yield strength and radial stiffness;

Crack formation/propagation/fracture when crimped and expanded by theballoon, or when implanted within a vessel and subjected to acombination of bending, axial crush and radial compressive loads;

Uniformity of deployment of scaffold rings when expanded by the balloon;and

Pinching/crushing stiffness.

Based on these studies, which have included in-vivo animal testing of aperipherally implanted scaffold, the invention provides the followingrelationships characterizing a polymer scaffold that exhibits thedesired characteristics including crush recoverability:

a ratio of outer diameter to wall thickness;

a ratio of outer diameter to strut width;

a ratio of radial stiffness to pinching stiffness;

a ratio of pinching stiffness to scaffold diameter;

a ratio of radial stiffness to scaffold diameter;

a ratio of strut or link thickness to its width; and

a ratio of pre-crimp scaffold diameter to strut moment of inertia.

Additional relationships characterizing mechanical properties of ascaffold meeting the above needs may be inferred from the disclosure.

According to one aspect of the invention, polymer scaffolds having crushrecovery and good radial strength and stiffness possess one or more ofthe following relations between material properties and/or scaffolddimensions. It will be understand that these relationships, as disclosedherein and throughout the disclosure, include previously unknownrelationships among scaffold structural properties, material anddimensions that reveal key characteristics of a scaffold needed for acrush-recoverable scaffold uniquely suited to achieve the clinicalobjective. As such, the invention includes the identification of aparticular relationship, e.g., a dimensionless number used incombination with one or more additional scaffold dimensions, e.g.,inflated diameter, aspect ratio, crown angle, wall thickness, to producea crush-recoverable scaffold having the desired stiffness and strengthproperty needed to support the vessel.

According to one aspect of the invention a strut forming a ring of thecrush recoverable scaffold has an aspect ratio (AR) of between about 0.8and 1.4. Aspect ratio (AR) is defined as the ratio of cross-sectionalwidth to thickness. Thus for a strut having a width of 0.0116 and a wallthickness of 0.011 the AR is 1.05.

According to another aspect of the invention, the links connect rings ofthe scaffold. The AR of a link may be between about 0.4 and 0.9.

According to another aspect of the invention, the AR of both the linkand the strut may between about 0.9 and 1.1, or about 1.

According to another aspect of the invention, a crush recoverablescaffold is crimped to a delivery balloon of a balloon catheter. Theballoon has a maximum expanded diameter less than the diameter of thescaffold before crimping. The scaffold has a pre-crimping diameter ofbetween 7-10 mm, or more narrowly 7-8 mm, and possesses a desiredpinching stiffness while retaining at least a 80% recoverability from a50% crush.

According to another aspect of the invention a crush-recoverablescaffold has a desirable pinching stiffness of at least 0.5 N/mm, radialstrength of at least 0.3 N/mm and a wall thickness of at least 0.008″,or between about 0.008″ and 0.012″. The scaffold is capable ofrecovering at least 80% of its diameter after at least an about 30%crush.

According to another aspect of invention a 9 mm scaffold (pre-crimpdiameter) with wall thickness of between 0.008″ and 0.014″, or morenarrowly 0.008″ and 0.011″ providing the desired pinching stiffnesswhile retaining 50% crush recoverability. More generally, it was foundthat a ratio of pre-crimp or tube diameter to wall thickness of betweenabout 30 and 60, or between about 20 and 45 provided 50% crushrecoverability while exhibiting a satisfactory pinching stiffness andradial stiffness. And in some embodiments it was found that a ratio ofinflated diameter to wall thickness of between about 25 and 50, orbetween about 20 and 35.

According to another aspect of the disclosure a crush-recoverablescaffold has a desirable pinching stiffness to wall thickness ratio of0.6-1.8 N/mm².

According to another aspect of the disclosure a crush-recoverablescaffold has a desirable pinching stiffness to wall thickness*tubediameter ratio of 0.08-0.18 N/mm³.

According to another aspect of invention a crush-recoverable scaffoldhas a ratios of pinching stiffness to radial stiffness of between about4 to 1, 3 to 1, or more narrowly about 2 to 1; ratios of pinchingstiffness to wall thickness of between about 10 to 70, or more narrowly20 to 50, or still more narrowly between about 25 and 50; and ratios ofscaffold inflated diameter to pinching stiffness of between about 15 and60 or more narrowly between about 20 to 40.

According to another aspect of the invention a crush recoverable polymerscaffold has rings comprising 9 or 8 crowns. For a 9 crown pattern and7-9 mm outer diameter a crown angle is less than 115 degrees and morepreferably crown angles between 105 and 95 degrees. For a 8 crownpattern and 7-9 mm outer diameter the angle is about less than 110degrees.

According to another aspect of invention, a crush-recoverable scaffoldhas a radial strength of greater than about 0.3 N/mm, or between about0.32 and 0.68 N/mm, and a radial stiffness of greater than about 0.5N/mm or between about 0.54 N/mm and 1.2 N/mm. The scaffold may have awall thickness of about 0.008″ to 0.014″ and configured for beingdeployed by a 6.5 mm non-compliant balloon from about a 2 mm crimpedprofile, or deployed to a diameter of between about 6.5 mm and 7 mm fromabout a 2 mm crossing profile on a balloon catheter. The scaffold strutand/or link elements may have an AR of equal to or greater than 1.0.

According to another aspect of the invention, a crush-recoverablepolymer scaffold recovers greater than 80% of its diameter after beingpinched to 50% of its diameter and the pinched state is maintained for1-5 minutes.

According to another aspect of the invention, a crush-recoverablepolymer scaffold recovers greater than 90% of its diameter after beingpinched to 25% of its diameter and the pinched state is maintained for1-5 minutes.

According to another aspect of the invention, a crush-recoverablepolymer scaffold includes a marker structure including a pair of markersarranged circumferentially on a connecting link and spaced from adjacentrings of the scaffold so that the crimped profile is the same with orwithout the markers. Alternatively, according to another aspect of theinvention, a radiopaque foil is wrapped around a link of the scaffoldand held in place

In another aspect of invention, a polymer scaffold having a wallthickness of between about 0.008″ and 0.014″ and outer diameter ofbetween about 7 mm and 10 mm was capable of meeting the foregoing needs.

In another aspect of the invention, a crush recoverable scaffold wascrimped from a 7 mm, 8 mm and 9 mm outer diameter to a 2 mm outerdiameter and deployed without fracture and/or excessive cracking ofstruts that are a typical concern when a polymer, especially a brittlepolymer like PLLA, is used to form the scaffold structure.

A scaffold has a pre-crimp diameter (SD_(PC)) meaning the diameter ofthe scaffold before it is crimped to its delivery balloon, and aninflated diameter (SD_(I)). The scaffold is crimped to theballoon-catheter and intended for delivery to a vessel within the body.The average vessel diameter where the scaffold is to be implanted is VD.SD_(I) is about 1.2 times greater than VD. For purposes of thedisclosure, VD can range from about 5 mm to 10 mm and SD_(PC) can rangebetween about 6 to 12 mm. According to another aspect of invention:1.1×(VD)≦SD _(PC)≦1.7×(VD)  (EQ.1)1.1×(SD _(I))×(1.2)⁻¹ ≦SD _(PC)≦1.7×(SD _(I))×(1.2)⁻¹  (EQ.2)

Scaffold satisfying EQS. 1 and 2 can yield a crush-recoverable scaffoldhaving at least 90% recovery after at least a 25% crush, while alsohaving favorable radial stiffness, pinching stiffness, acceptablerecoil, radial strength and/or crossing profile. In a preferredembodiment the scaffold is made from PLLA. The partial inequalities inEQS. 1 and 2 are intended to refer to approximate ranges.

It is contemplated that a polymer scaffold according to the inventionmay be used to treat conditions in the Femoral artery, Popliteal artery,Tibial artery, Pudendal artery, Brachial artery, Carotid artery, Jugularvein, Abdominal arteries and veins.

In another aspect of the invention a symmetric, closed cell for ascaffold improves deployment uniformity and reduces fracture problemsfor a scaffold having crush recoverability.

In another aspect of invention a balloon-expandable medical device forbeing implanted in a peripheral vessel of the body includes a scaffoldformed from a polymer tube,—configured for being crimped to aballoon,—the scaffold having a pattern of interconnected elementsand—the scaffold having an expanded diameter when expanded from acrimped state by the balloon, wherein the scaffold attains greater thanabout 90% of its diameter after being crushed to at least 33% of itsexpanded diameter; and wherein the scaffold has a radial stiffnessgreater than 0.3 N/mm.

In another aspect of invention a balloon-expandable medical device forbeing implanted in a peripheral vessel of the body includes a crimpedscaffold that when deployed by a balloon forms a scaffold having anexpanded diameter; wherein the scaffold is capable of regaining morethan 90% of its diameter after being crushed to at least 75% of itsexpanded diameter; and wherein the scaffold comprises—a radial stiffnessgreater than about 0.3 N/mm, and—a radial strength, pinching strength,pinching stiffness and fracture toughness of a pre-crimp scaffold havinga pre-crimp diameter between 300-400% greater than a diameter of thecrimped scaffold.

In another aspect of invention a radially expandable stent includes aballoon expandable scaffold formed from a PLLA tube,—the scaffoldincluding a plurality of radially expandable undulating cylindricalrings of struts, wherein the undulating rings of struts comprise crowns,wherein adjacent rings of struts are connected by longitudinal links,wherein a ring has no more than 9 crowns and 3 links around itscircumference, and the angle at any crown is less than 115 degrees;—thescaffold has an outer diameter of 8 to 10 mm; and—the scaffold has awall thickness at least about 0.008″.

In another aspect of invention a peripherally implantable medical deviceincludes a crimped scaffold that when expanded by a balloon forms ascaffold having a diameter;—the scaffold regains more than 90% of thediameter after being crushed to at least 67% of the diameter,—thescaffold is formed from PLLA,—the scaffold has a diameter to wallthickness ratio of between about 30 and 60;—the scaffold has struts andlinks, wherein a strut and/or link has a width to thickness ratio ofbetween about 0.8 and 1.4, and—the scaffold has a radial stiffnessgreater than or equal to about 0.3 N/mm.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference, and as if eachsaid individual publication or patent application was fully set forth,including any figures, herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a deformed polymer tube. The tube isformed into a scaffold.

FIG. 2 is a partial planar view of a scaffold pattern according to afirst embodiment of a scaffold.

FIG. 3 is a partial perspective view of a scaffold structure.

FIG. 4 is a partial planar view of a scaffold pattern according to asecond embodiment of a scaffold.

FIG. 5A is a planar view of a portion of the scaffold pattern of FIG. 4taken at section VA-VA.

FIG. 5B is a planar view of a portion of the scaffold pattern of FIG. 2taken at section VB-VB.

FIGS. 6A and 6B are tables showing examples of scaffold features inaccordance with aspects of the disclosure.

FIG. 7A-7B shows a scaffold crown formation in its expanded and crimpedstates.

FIG. 7C-7D shows a scaffold crown formation in its expanded and crimpedstates for a scaffold according to the first embodiment.

FIG. 7E-7F shows a scaffold crown formation in its expanded and crimpedstates for a scaffold according to an alternative embodiment.

FIGS. 8B, 8C and 8D are scanning electron microscope (SEM) photographsof scaffold crowns. The crowns have an inner radius of about 0.00025inches. The photographs are taken after the scaffold was expanded by aballoon.

FIGS. 8A, 8F and 8G are scanning electron microscope (SEM) photographsof scaffold crowns having an inner radius substantially higher than theinner radius of the scaffold crowns in FIGS. 8B, 8C and 8D. Thephotographs are taken after the scaffold was expanded by a balloon. FIG.8E is another scanning electron microscope (SEM) photographs of ascaffold crown.

FIGS. 9A-9B show the first embodiment of a scaffold including aradiopaque marker structure formed on a link connecting rings. FIG. 9Ashows the expanded configuration and FIG. 9B shows the location of theradiopaque markers relative to folded struts of the scaffold rings inthe crimped configuration.

FIGS. 10A-10B show an alternative embodiment of a scaffold including aradiopaque marker disposed on a link connecting rings. FIG. 10A showsthe expanded configuration and FIG. 10B shows the location of theradiopaque marker relative to folded struts of the scaffold rings in thecrimped configuration.

FIGS. 11A-11E are several alternative embodiments of a scaffoldincluding a radiopaque marker. For these embodiments the radiopaquemarker(s) are located on or near the crown of a crown, as opposed to ona link connecting rings. FIGS. 11A, 11B and 11E depict examples oflocations for a cylindrical marker while FIGS. 11C and 11D depictlocations for a strip of marker material.

FIG. 11F depicts an alternative embodiment of a scaffold having aradiopaque marker. In this example the radiopacity is provided throughmaterial used to strengthen the crown at an end ring. As such, theembodiments provide more visibility at the end ring while alsostrengthening the end ring.

FIGS. 12A, 12B and 12C are diagrams describing a relationship betweencrush recoverability and wall thickness for a scaffold. FIG. 12A shows across-section of a scaffold in its un-deformed (unloaded) state anddeformed state when subjected to a pinching load (drawn in phantom).FIGS. 12B-12C are models of equivalent half-cylinder shells of differentthickness to show the effects of wall thickness on crush-recoverabilitywhen a scaffold is subject a pinching load.

FIG. 13 is a plot showing the crush-recovery for a scaffold after a 50%crush. The plot shows the percentage recovered over a 24 hour periodfollowing a brief, 1 minute and 5 minute crush at 50%.

FIGS. 14A and 14B are partial planar views of a scaffold patternaccording to an alternate embodiment of a scaffold including a firstembodiment of a weakened or flexible link element connecting rings.

FIG. 14C is a second embodiment of a weakened or flexible link elementconnecting rings of the scaffold.

FIGS. 14D and 14F shows an alternate embodiment of a weakened portion ofa link connecting rings. FIG. 14D shows an asymmetric weakened linkportion and FIG. 14F shows a symmetric weakened link portion.

FIG. 14E shows an example of a link structure where voids are formed inthe link to create a point of fracture for the link at the voids.

FIG. 15 is a partial planar view of a scaffold pattern according to analternate ring structure for a scaffold where the ring structure hascurved struts extending between crowns.

FIGS. 16-23 are plots showing results from a first animal study for animplanted scaffold at 30, 90 and 180 days following implantation. Thescaffold performance is compared to a self-expanding metal stentimplanted within the same animal.

FIGS. 24-26 are plots showing results from a second animal studycomparing the performance of scaffold having different wall thickness.

DETAILED DESCRIPTION OF EMBODIMENTS

The disclosure proceeds as follows. First, definitions of terms that maybe used during the course of the subsequent disclosure are explained.Embodiments of processes for forming a deformed polymer tube from aprecursor are provided. According to the disclosure, the crushrecoverable and balloon expandable scaffold is cut from a tube (FIG. 1)formed through a process intended to enhance mechanical properties ofthe scaffold including fracture toughness. Discussion of the scaffoldpatterns according to several embodiments are discussed next. Examplesof the scaffold patterns are provided. During this discussion, referenceis made to aspects of a scaffold found to play an important role in thestiffness, strength, crimping and deployment of a polymer scaffold, aswell as other properties as they relate to crush recoverability of aload-bearing polymer structure. Included herein are aspects of thescaffold that are contrary and, in some cases, surprising andunexpected, particularly when compared to aspects of a comparable,peripheral metal stent having a similar pattern of struts. Finally,bench and in-vivo test results are discussed, including exemplaryexamples of embodiments of invention and explanation of the resultsobserved and problems overcome. In these examples there may be gained afurther appreciation of aspects of invention—a crush recoverable andballoon-expandable polymer scaffold having desirable radial strength andstiffness properties and capable of being crimped to a diameter suitablefor delivery through a blood vessel via a balloon catheter.

For purposes of this disclosure, the following terms and definitionsapply:

“Inflated diameter” or “expanded diameter” refers to the maximumdiameter the scaffold attains when its supporting balloon is inflated toexpand the scaffold from its crimped configuration to implant thescaffold within a vessel. The inflated diameter may refer to apost-dilation diameter which is beyond the nominal balloon diameter,e.g., a 6.5 mm semi-compliant PEBAX balloon has about a 7.4 mmpost-dilation diameter. The scaffold diameter, after attaining itsinflated diameter by balloon pressure, will to some degree decrease indiameter due to recoil effects and/or compressive forces imposed by thewall of the vessel after the balloon is removed. For instance, referringto an expansion of the V59 scaffold having the properties in Table 6B,when placed on a 6.5 mm PEBAX balloon and the balloon is expanded to apost-dilation condition outside a vessel, the scaffold inner diameterwill be about 7.4 mm and about (0.955)×(7.4 mm) before and after,respectively, acute-recoil has occurred. The inflated diameter may beabout 1.2 times the average vessel diameter and peripheral vessel sizestypically range from about 4 to 10 mm for purposes of this disclosure.

“Theoretical minimum diameter” means the smallest diameter for ascaffold based on its geometry of strut lengths, thickness and widths. A“theoretical minimum diameter” is not defined in terms of a minimumcrimped profile for a scaffold or stent that can be later deployed andwork properly as a balloon-expanded prosthesis. Rather, it is only adefinition defined by the geometry, or minimum volume of space that adevice can occupy following a uniform reduction in diameter. As aformula, the “theoretical minimum diameter” (Dmin) may be expressed asfollows:Dmin=(ΣSwi+ΣCrj+ΣLwk)*(1/π)+2*WT  (EQ.3)

Where the quantities above are taken from a cross-sectional slice of thescaffold,

ΣSwi (i=1 . . . n) is the sum of n ring struts having width Swi;

ΣCrj (j=1 . . . m) is the sum of m crown inner radii having radii Crj(times 2);

ΣLwk (k=1 . . . p) is the sum of p links having width Lwk; and

WT is the scaffold wall thickness.

EQ. 3 assumes the width for a folded pair of struts, e.g., struts 420,422 in FIG. 7A, is the same whether measured near the crown 410 or thestrut mid width. When the crown is built up more, so that the width iswider there than ring strut mid-width, Swi would be measured by thewidth at the crown. Also, the minimum space between struts is defined bytwice the inner radius of the adjacent crown (or valley), i.e., Crj.

For the scaffold dimensions of FIG. 6B the crown width is wider than thestrut mid-width. Therefore, using EQ. 3 Dmin is[16*(0.013)+12*(0.0005)+4*(0.0115)]*(1/π)+2*(0.011)=0.1048″ or 2.662 mm(minimum diameter computed at cross-section passing through crowns). If,instead the cross-section were taken at the strut mid width (0.0116instead of 0.013) EQ. 3 gives 0.0976″ or 2.479 mm.

It should be noted that EQ.3 assumes the struts have essentially asquare cross-section. This is the case for the scaffold of FIG. 6B(strut cross-sectional dimension at the crown is 0.011×0.013). For ascaffold having struts with a trapezoidal cross section, e.g., ascaffold cut from a smaller diameter so that the ratio of wall thicknessto outer diameter is much higher than in the case of FIG. 1, a moreaccurate approximation for Dmin would be (ΣSwi+ΣCrj+ΣLwk)*(1/π) sincethe edges of the struts at the outer surface would abut at Dmin beforethe surfaces extending over the thickness of a strut abut each other.

The glass transition temperature (referred to herein as “Tg”) is thetemperature at which the amorphous domains of a polymer change from abrittle vitreous state to a solid deformable or ductile state atatmospheric pressure. In other words, Tg corresponds to the temperaturewhere the onset of segmental motion in the chains of the polymer occurs.Tg of a given polymer can be dependent on the heating rate and can beinfluenced by the thermal history of the polymer. Furthermore, thechemical structure of the polymer heavily influences the glasstransition by affecting mobility of polymer chains.

“Stress” refers to force per unit area, as in the force acting through asmall area within a plane within a subject material. Stress can bedivided into components, normal and parallel to the plane, called normalstress and shear stress, respectively. Tensile stress, for example, is anormal component of stress that leads to expansion (increase in length)of the subject material. In addition, compressive stress is a normalcomponent of stress resulting in compaction (decrease in length) of thesubject material.

“Strain” refers to the amount of expansion or compression that occurs ina material at a given stress or load. Strain may be expressed as afraction or percentage of the original length, i.e., the change inlength divided by the original length. Strain, therefore, is positivefor expansion and negative for compression.

“Modulus” may be defined as the ratio of a component of stress or forceper unit area applied to a material divided by the strain along an axisof applied force that result from the applied force. For example, amaterial has both a tensile and a compressive modulus.

“Toughness”, or “fracture toughness” is the amount of energy absorbedprior to fracture, or equivalently, the amount of work required tofracture a material. One measure of toughness is the area under astress-strain curve from zero strain to the strain at fracture. Thestress is proportional to the tensile force on the material and thestrain is proportional to its length. The area under the curve then isproportional to the integral of the force over the distance the polymerstretches before breaking. This integral is the work (energy) requiredto break the sample. The toughness is a measure of the energy a samplecan absorb before it breaks. There is a difference between toughness andstrength. A material that is strong, but not tough is said to bebrittle. Brittle materials are strong, but cannot deform very muchbefore breaking.

As used herein, the terms “axial” and “longitudinal” are usedinterchangeably and refer to a direction, orientation, or line that isparallel or substantially parallel to the central axis of a stent or thecentral axis of a tubular construct. The term “circumferential” refersto the direction along a circumference of the stent or tubularconstruct. The term “radial” refers to a direction, orientation, or linethat is perpendicular or substantially perpendicular to the central axisof the stent or the central axis of a tubular construct and is sometimesused to describe a circumferential property, i.e. radial strength.

The term “crush recovery” is used to describe how the scaffold recoversfrom a pinch or crush load, while the term “crush resistance” is used todescribe the force required to cause a permanent deformation of ascaffold. A scaffold or stent that does not possess good crush recoverydoes not substantially return to its original diameter following removalof a crushing force. As noted earlier, a scaffold or stent having adesired radial force can have an unacceptable crush recovery. And ascaffold or stent having a desired crush recovery can have anunacceptable radial force.

The polymer scaffold illustrated in FIG. 2 is formed from apoly(L-lactide) (“PLLA”) tube. The process for forming this PLLA tubemay be the process described in U.S. patent application Ser. No.12/558,105. Reference is made to a precursor that is “deformed” in orderto produce the tube of FIG. 1 having the desired scaffold diameter,thickness and material properties as set forth below. Before the tube isdeformed or, in some embodiments, expanded to produce the desiredproperties in the starting tube for the scaffold, the precursor isformed. The precursor may be formed by an extrusion process which startswith raw PLLA resin material heated above the melt temperature of thepolymer which is then extruded through a die. Then, in one example, anexpansion process for forming an expanded PLLA tube includes heating aPLLA precursor above the PLLA glass transition temperature (i.e., 60-70degrees C.) but below the melt temperature (165-175 degrees C.), e.g.,around 110-120 degrees C.

A precursor tube is deformed in radial and axial directions by a blowmolding process wherein deformation occurs progressively at apredetermined longitudinal speed along the longitudinal axis of thetube. As explained below, the deformation improves the mechanicalproperties of the tube before it is formed into the scaffold of FIG. 2.The tube deformation process is intended to orient polymer chains inradial and/or biaxial directions. The orientation or deformation causingre-alignment is performed according to a precise selection of processingparameters, e.g. pressure, heat (i.e., temperature), deformation rate,to affect material crystallinity and type of crystalline formationduring the deformation process.

In an alternative embodiment the tube may be made ofpoly(L-lactide-co-glycolide), poly(D-lactide-co-glycolide) (“PLGA”),polycaprolactone (“PCL”), any semi-crystalline copolymers combining anyof these monomers, or any blends of these polymers. Material choices forthe scaffold should take into consideration the complex loadingenvironment associated with many peripheral vessel locations,particularly those located close to limbs.

The femoral artery provides a dynamic environment for vascular implantsas various forces may crush, twist, extend, or shorten the devicesimultaneously. The force application may vary between point load todistributed load or a combination thereof and also as a function oftime. Recent results have shown that bioresorbable scaffolds made fromhighly crystalline PLLA can provide crush recovery without causing apermanent and constant outward radial force on the vessel. The permanentand constant outward radial force may be the cause of late clinicalissues with nitinol self-expandable stents. However, a remainingchallenge with bioresorbable scaffolds is to make them optimallyfracture resistant as a function of time; that is, to improve theirfatigue life or survivability under a variety of dynamic loadingenvironments. There is a continuing need to improve fracture toughnessfor a scaffold; and in particular a peripherally implanted scaffold.

The fracture resistance of a vascular scaffold depends not only on thedesign and the material, but is also the manufacturing process anddeployment parameters. Therefore it is in particular necessary to have aprocess, design, and a delivery system that allows the scaffold to beuniformly expanded and deployed. As a consequence of non-uniformdeployment the various struts and crowns of a scaffold will potentiallybe exposed to very different forces and motions, which has a deleteriouseffect on the fatigue life.

An useful dimensionless number useful for characterizing a material'sfracture toughness is called a Deborah number (Ratio of intrinsicmaterial damping time constant and time constant of external appliedforce). The higher the Deborah number, the greater is the expectedpotential of an implant to fracture under a transient load or fatigueload of a given amplitude.

Toughening domains can be introduced into an implant design in severalways: a) backbone alteration to include low Tg blocks, e.g. blockcopolymers, b) polymer blends and c) introducing light crosslinks intothe backbone.

Fracture toughness of a homopolymer such as PLLA can also be improved bycontrolling the microstructure of the final implant. Variables such as %crystallinity, size and/or distribution of crystallites, spatialdistribution, and gradient and shape of the crystalline domains. Acombination of these micro-structural controls in combination with amacroscopic design, e.g., scaffold pattern, crimping process, etc. mayimprove fracture toughness without significant adverse affects on otherscaffold material properties, e.g., radial and/or pinching stiffness.

An alternative to providing elastomeric properties is the use of amultilayered structure having “soft” and “hard” layers, where the softlayer/layers would be made from a low Tg material and the hard layerswould have a high Tg material. In a similar way high and low Tg domainscan generate typical rubber-toughened morphologies through the use ofblock copolymers or polymer blends. The Tg of a given domain/block couldbe generated from a given monomer or by the use of several monomers in arandom co-polymer. Typical low Tg materials can be made fromcaprolactone, lactone derivatives, carbonate, butylsuccinate,trimethylene carbonate, dioxanone or other known monomers in accordancewith the disclosure. Other low Tg materials that could be used, would bea material that clears the kidneys through dissolution rather thandegradation. Such material may include polyethylene glycol (PEG),polyvinylpyrrolidone (PVP), or polyvinylalochol (PVA), or other knownpolymers in accordance with the disclosure.

Alternative ways to improve the fatigue properties are throughintroduction of axial flexibility and the use of pre-designed fracturepoints, in particular in the connector links. The fracture points couldfunction as precursors of actual fractures, e.g., crazes and cracks orsmall dimension of fracture distributed in the implant. A distributionor pattern of cracks or crazes may dictate or inform one of an expectedtoughness of the scaffold when subjected to a particular loading, e.g.,torsion, radial force, tensile etc. Although it is understood that, dueto the generally highly non-linear relationship between crack formationand a coupled loading environment, that is, simultaneously applied andtime varying bending, torsion and axial loading, such predictive methodsmay not be applicable to all situations.

Alternative ways to improve the fatigue properties are throughintroduction of axial flexibility and the use of pre-designed fracturepoints, in particular, fracture points in or near connector links asdiscussed in greater detail below.

For a tube of FIG. 1 having a diameter about 7 mm and a wall thicknessabove 200 micro-meters and more specifically a diameter of 8 mm and awall thickness of 280 micro-meters, the temperature at expansion is235+/−5 degrees Fahrenheit, the expansion pressure is 110+/−10 psi andthe expansion speed is 0.68+/−0.20 mm/sec.

The degree of radial expansion that the polymer tube undergoes canpartially characterize the degree of induced circumferential molecularand crystal orientation as well as strength in a circumferentialdirection. The degree of radial expansion is quantified by a radialexpansion (“RE”) ratio, defined as RE Ratio=(Inside Diameter of ExpandedTube)/(Original Inside Diameter of the tube). The RE ratio can also beexpressed as a percentage, defined as RE %=(RE ratio−1).times.100%. Thedegree of axial extension that the polymer tube undergoes can partiallycharacterize induced axial molecular or crystal orientation as well asstrength in an axial direction. The degree of axial extension isquantified by an axial extension (“AE”) ratio, defined as AERatio=(Length of Extended Tube)/(Original Length of the Tube). The AEratio can also be expressed as a percentage, defined as AE %=(AEratio−1).times.100%. In a preferred embodiment the RE is about 400% andthe AE is 40-50%.

The strengthened and toughened cylindrical, polymer tube of FIG. 1 isformed into a scaffold structure, in one embodiment a structure having aplurality of struts 230 and links 234 forming a pattern 200 as shown inFIG. 2 (pattern 200 is illustrated in a planar or flattened view), whichis about the pattern for the scaffold before crimping and after thescaffold is plastically, or irreversibly deformed from its crimped stateto its deployed state within a vessel by balloon expansion. The pattern200 of FIG. 2, therefore, represents a tubular scaffold structure (aspartially shown in three dimensional space in FIG. 3), so that an axisA-A is parallel to the central or longitudinal axis of the scaffold.FIG. 3 shows the scaffold in a state prior to crimping or afterdeployment. As can be seen from FIG. 3, the scaffold comprises an openframework of struts and links that define a generally tubular body. Thecylindrical, deformed tube of FIG. 1 may be formed into this openframework of struts and links described in FIGS. 2-3 by a laser cuttingdevice, preferably, a pico-second green light laser that uses Helium gasas a coolant during cutting.

Details of a suitable laser process can be found in U.S. applicationSer. No. 12/797,950. The Helium gas is necessary to avoid melting oraltering properties of the scaffold structure adjacent the laser'scutting path. Exemplary laser machining parameters are provided in Table1.

TABLE 1 Laser Machining Parameters for a crush recoverable polymerscaffold having a wall thickness of between about .008″ and .014″Parameter Range Scaffold length (mm)  8-200 No. of passes to cut 2-4Cutting speed (in/min)  4-10 Fast jog speed (in/min) 10-14 Maxaccel/decal (in/min²) 0-6 Tube outer diameter  6-12 Laser spot size14-20 Laser rep rate (kHz) 25-50 Laser power setting (W)  .8-1.22 Heliumgas flow (scfh) 11-17

Referring to FIG. 2, the pattern 200 includes longitudinally-spacedrings 212 formed by struts 230. A ring 212 is connected to an adjacentring by several links 234, each of which extends parallel to axis A-A.In this first embodiment of a scaffold pattern (pattern 200) four links234 connect the interior ring 212, which refers to a ring having a ringto its left and right in FIG. 2, to each of the two adjacent rings.Thus, ring 212 b is connected by four links 234 to ring 212 c and fourlinks 234 to ring 212 a. Ring 212 d is an end ring connected to only thering to its left in FIG. 2.

A ring 212 is formed by struts 230 connected at crowns 207, 209 and 210.A link 234 is joined with struts 230 at a crown 209 (W-crown) and at acrown 210 (Y-crown). A crown 207 (free-crown) does not have a link 234connected to it. Preferably the struts 230 that extend from a crown 207,209 and 210 at a constant angle from the crown center, i.e., the rings212 are approximately zig-zag in shape, as opposed to sinusoidal forpattern 200, although in other embodiments a ring having curved strutsis contemplated. As such, in this embodiment a ring 212 height, which isthe longitudinal distance between adjacent crowns 207 and 209/210 may bederived from the lengths of the two struts 230 connecting at the crownand a crown angle θ. In some embodiments the angle θ at different crownswill vary, depending on whether a link 234 is connected to a free orunconnected crown, W-crown or Y-crown.

The zig-zag variation of the rings 212 occurs primarily about thecircumference of the scaffold (i.e., along direction B-B in FIG. 2). Thestruts 212 centroidal axes lie primarily at about the same radialdistance from the scaffold's longitudinal axis. Ideally, substantiallyall relative movement among struts forming rings also occurs axially,but not radially, during crimping and deployment. Although, as explainedin greater detail, below, polymer scaffolds often times do not deform inthis manner due to misalignments and/or uneven radial loads beingapplied.

The rings 212 are capable of being collapsed to a smaller diameterduring crimping and expanded to a larger diameter during deployment in avessel. According to one aspect of the disclosure, the pre-crimpdiameter (e.g., the diameter of the axially and radially expanded tubefrom which the scaffold is cut) is always greater than a maximumexpanded scaffold diameter that the delivery balloon can, or is capableof producing when inflated. According to one embodiment, a pre-crimpdiameter is greater than the scaffold expanded diameter, even when thedelivery balloon is hyper-inflated, or inflated beyond its maximum usediameter for the balloon-catheter.

Pattern 200 includes four links 237 (two at each end, only one end shownin FIG. 2) having structure formed to receive a radiopaque material ineach of a pair of transversely-spaced holes formed by the link 237.These links are constructed in such a manner as to avoid interferingwith the folding of struts over the link during crimping, which, asexplained in greater detail below, is necessary for a scaffold capableof being crimped to a diameter of about at most Dmin or for a scaffoldthat when crimped has virtually no space available for a radiopaquemarker-holding structure.

A second embodiment of a scaffold structure has the pattern 300illustrated in FIG. 4. Like the pattern 200, the pattern 300 includeslongitudinally-spaced rings 312 formed by struts 330. A ring 312 isconnected to an adjacent ring by several links 334, each of whichextends parallel to axis A-A. The description of the structureassociated with rings 212, struts 230, links 234, and crowns 207, 209,210 in connection with FIG. 2, above, also applies to the respectiverings 312, struts 330, links 334 and crowns 307, 309 and 310 of thesecond embodiment, except that in the second embodiment there are onlythree struts 334 connecting each adjacent pair of rings, rather thanfour. Thus, in the second embodiment the ring 312 b is connected to thering 312 c by only three links 234 and to the ring 312 a by only threelinks 334. A link formed to receive a radiopaque marker, similar to link237, may be included between 312 c and ring 312 d.

FIGS. 5A and 5B depict aspects of the repeating pattern of closed cellelements associated with each of the patterns 300 and 200, respectively.FIG. 5A shows the portion of pattern 300 bounded by the phantom box VAand FIG. 5B shows the portion of pattern 200 bounded by the phantom boxVB. Therein are shown cell 304 and cell 204, respectively. In FIGS. 5A,5B the vertical axis reference is indicated by the axis B-B and thelongitudinal axis A-A. There are four cells 204 formed by each pair ofrings 212 in pattern 200, e.g., four cells 204 are formed by rings 212 band 212 c and the links 234 connecting this ring pair, another fourcells 204 are formed by rings 212 a and 212 b and the links connectingthis ring pair, etc. In contrast, there are three cells 304 formed by aring pair and their connecting links in pattern 300.

Referring to FIG. 5A, the space 336 and 336 a of cell 304 is bounded bythe longitudinally spaced rings 312 b and 312 c portions shown, and thecircumferentially spaced and parallel links 334 a and 334 c connectingrings 312 b and 312 c. Links 334 b and 334 d connect the cell 304 to theright and left adjacent ring in FIG. 3, respectively. Link 334 bconnects to cell 304 at a W-crown 309. Link 334 d connects to cell 304at a Y-crown 310. A “Y-crown” refers to a crown where the angleextending between a strut 330 and the link 334 at the crown 310 is anobtuse angle (greater than 90 degrees). A “W-crown” refers to a crownwhere the angle extending between a strut 330 and the link 334 at thecrown 309 is an acute angle (less than 90 degrees). The same definitionsfor Y-crown and W-crown also apply to the cell 204. There are eightconnected or free crowns 307 for cell 304, which may be understood aseight crowns devoid of a link 334 connected at the crown. There are oneor three free crowns between a Y-crown and W-crown for the cell 304.

Additional aspects of the cell 304 of FIG. 5A include angles for therespective crowns 307, 309 and 310. Those angles, which are in generalnot equal to each other (see e.g., FIG. 6A for the “V2” and “V23”embodiments of scaffold having the pattern 300), are indentified in FIG.5A as angles 366, 367 and 368, respectively associated with crowns 307,309 and 310. For the scaffold having the pattern 300 the struts 330 havestrut widths 361 and strut lengths 364, the crowns 307, 309, 310 havecrown widths 362, and the links 334 have link widths 363. Each of therings 312 has a ring height 365. The radii at the crowns are, ingeneral, not equal to each other. The radii of the crowns are identifiedin FIG. 5A as radii 369, 370, 371, 372, 373 and 374.

Cell 304 may be thought of as a W-V closed cell element. The “V” portionrefers to the shaded area 336 a that resembles the letter “V” in FIG.6A. The remaining un-shaded portion 336, i.e., the “W” portion,resembles the letter “W”.

Referring to FIG. 5B, the space 236 of cell 204 is bounded by theportions of longitudinally spaced rings 212 b and 212 c as shown, andthe circumferentially spaced and parallel links 234 a and 234 cconnecting these rings. Links 234 b and 234 d connect the cell 204 tothe right and left adjacent rings in FIG. 2, respectively. Link 234 bconnects to cell 236 at a W-crown 209. Link 234 d connects to cell 236at a Y-crown 210. There are four crowns 207 for cell 204, which may beunderstood as four crowns devoid of a link 234 connected at the crown.There is only one free crown between each Y-crown and W-crown for thecell 204.

Additional aspects of the cell 204 of FIG. 5B include angles for therespective crowns 207, 209 and 210. Those angles, which are in generalnot equal to each other (see e.g., FIG. 6B for the “V59” embodiment of ascaffold having the pattern 200), are indentified in FIG. 5B as angles267, 269 and 268, respectively associated with crowns 207, 209 and 210.For the scaffold having the pattern 200 the struts 230 have strut widths261 and strut lengths 266, the crowns 207, 209, 210 have crown widths270, and the links 234 have link widths 264. Each of the rings 212 has aring height 265. The radii at the crowns are, in general, not equal toeach other. The radii of the crowns are identified in FIG. 5B as innerradii 262 and outer radii 263.

Cell 204 may be thought of as a W closed cell element. The space 236bounded by the cell 204 resembles the letter “W”.

Comparing FIG. 5A to FIG. 5B one can appreciate that the W cell 204 issymmetric about the axes B-B and A-A whereas the W-V cell 304 isasymmetric about both of these axes. The W cell 204 is characterized ashaving no more than one crown 207 between links 234. Thus, a Y-crowncrown or W-crown is always between each crown 207 for each closed cellof pattern 200. In this sense, pattern 200 may be understood as havingrepeating closed cell patterns, each having no more than one crown thatis not supported by a link 234. In contrast, the W-V cell 304 has threeunsupported crowns 307 between a W-crown and a Y-crown. As can beappreciated from FIG. 5A, there are three unsupported crowns 307 to theleft of link 334 d and three unsupported crowns 307 to the right of link334 b.

The mechanical behavior of a scaffold having a pattern 200 verses 300differs in the following ways. These differences, along with others tobe discussed later, have been observed in comparisons between thescaffold of FIGS. 6A-6B, which include in-vivo testing. In certainregards, these tests demonstrated mechanical aspects of scaffoldaccording to the invention that were both unexpected and contrary toconventional wisdom, such as when the conventional wisdom originatedfrom state of the art metallic stents, or coronary scaffold. For aparticular design choice, whether driven by a clinical, productionyield, and/or delivery profile requirement, therefore, the followingcharacteristics should be kept in mind.

In general, a polymer scaffold that is crush-recoverable, possesses adesired radial stiffness and strength, fracture toughness and is capableof being crimped down to a target delivery diameter, e.g., at leastabout Dmin, balances the three competing design attributes of radialstrength/stiffness verses toughness, in-vivo performance versescompactness for delivery to a vessel site, and crush recovery versesradial strength/stiffness.

In-vivo performance verses compactness for delivery to the vessel siterefers to the ability to crimp the scaffold down to the deliverydiameter. The ring struts 230 connecting crowns to form the W-cell 204are more restrained from rotating about an axis tangent to the abluminalsurface (axis A-A). In the case of the W-V cell the V portion, the crownmay tend to twist about the axis A-A under particular configurations dueto the reduced number of connecting links 336. The ring portions can ineffect “flip”, which means rotate or deflects out-of-plane as a resultof buckling (please note: “out-of-plane” refers to deflections outsideof the arcuate, cylindrical-like surface of the scaffold; referring toFIG. 5A “out-of-plane” means a strut that deflects normal to the surfaceof this figure). When there is a link 234 at each of a crown or valleyas in FIG. 5B, any tendency for the crown to buckle or flip is reducedbecause the ring struts are more restrained by the link 236.Essentially, the link serves to balance the load across a ring moreevenly.

The “flipping” phenomenon for a scaffold constructed according topattern 300 has been observed during crimping, as explained andillustrated in greater detail in U.S. application Ser. No. 12/861,719.The W-V cell 304 is devoid of a nearby link 334 at a crown 307 torestrain excessive twisting of the adjacent crown or valley. In essence,when there are two crowns 307 between a link 334 the restraintpreventing flipping or buckling of the V portion of the ring depends onthe buckling strength of the individual ring strut 330, i.e., thestrength and stiffness of the polymer strut in torsion. When there is alink 234 connected to each adjacent crown/valley (FIG. 5B), however, outof plane deflections at the crown 207 is restrained more, due to thebending stiffness added by the connected link 234, which restrainstwisting at the adjacent crown 207.

A scaffold according to pattern 200 is correspondingly stiffer than asimilarly constructed scaffold according to pattern 300. The scaffoldaccording to pattern 200 will be stiffer both axially and inlongitudinal bending, since there are more links 236 used. Increasedstiffness may not, however, be desirable. Greater stiffness can producegreater crack formation over a less stiff scaffold. For example, thestiffness added by the additional links can induce more stress on ringsinterconnected by the additional links 234, especially when the scaffoldis subjected to a combined bending (rings moving relative to each other)and radial compression and/or pinching (crushing). The presence of thelink 234 introduces an additional load path into a ring, in addition tomaking the ring more stiff.

In-vivo requirements can favor a scaffold according to pattern 200, buta scaffold according to pattern 300 may be more easily crimped down tothe delivery diameter. Other factors also affect the ability to crimp ascaffold. According to the disclosure, it was found that crown anglesless than about 115 degrees for the pre-crimp scaffold can produce lessfracture and related deployment problems (e.g., uneven folding/unfoldingof ring struts) than scaffold with higher crown angles (relative to theinflated diameter, in one case 6.5 mm). The scaffold is crimped to aballoon that can be inflated up to about 7.4 mm. Thus, when the balloonis hyper-inflated the scaffold attains about up to about a 7 mm inflateddiameter. For a balloon catheter-scaffold assembly according to thedisclosure the largest inflated diameter for the balloon is less than orequal to the scaffold diameter before crimping. As mentioned above, itis preferred that the maximum inflated diameter for the scaffold is lessthan the scaffold diameter before crimping.

During the course of designing a crush recoverable polymer scaffoldhaving a desired crimped profile, it was found that when forming thescaffold at the 8 mm diameter it was difficult to crimp the scaffold toa desired crimped profile, e.g., to crimp the scaffold from the 8 mmdiameter to about 2 mm profile, for two reasons. First, by imposing the350-400% diameter reduction requirement, the polymer material was moresusceptible to crack formation and propagation, simply due to strainlevels experienced by the scaffold when subjected to this extensivediameter reduction. This concern was addressed by adjusting stiffness,e.g., reducing the strut angle, wall thickness and/or number of crowns.Additionally, the process steps used to form the tube (FIG. 1) was foundto help improve the scaffold's resistance to crack formation andpropagation, as explained earlier.

Second, even when the scaffold dimensions were adjusted to limit crackformation, there was the problem of limited space for scaffold withinthe crimped profile. Due to the mass of material associated with thecrimped scaffold, the available space for compression of the rings tothe desired crimped profile was not achievable without creatingunacceptable yield stresses or fracture. Thus, even when a 350-400%diameter reduction was achievable without crack or deployment problems,the scaffold pattern would not allow further reduction without exceedingthe range of articulation that the scaffold design would allow.

According to another aspect of the disclosure, there are modified crowndesigns for a scaffold intended to improve the fracture toughness and/orreduce the delivery diameter of the scaffold. It was discovered that adesign change to an existing scaffold pattern that would overcome alimitation on reduced profile, and which could be implemented using abrittle polymer like PLLA of PLGA, was a significant reduction in thesize of the inner radius of the crown or valley bridging the struts thatform the crown/valley.

FIGS. 7A and 7B illustrate a pair of struts 420, 422 near a crown 410.In the pre-crimp state, the struts 420, 422 are separated by the crownangle φ and the crown is formed with an inner radius r_(a). This is atypical design for a crown. The inner radius is selected to avoid stressconcentrations at the crown. As the art has taught when there is adramatic change in geometry at a hinge point, such as a crown, there isa greater likelihood cracks or yielding will form at the hinge point(thereby affecting radial strength) since the moment of inertia inbending across the crown is discontinuous.

In the case of a metal stent, the angle φ before crimping is less thanthe angle when the stent is deployed. By forming the stent with thereduced diameter, the stent may be more easily crimped to a smallprofile. Due to the presence of the inner radius, the angle φ is capableof being exceeded at deployment without loss of radial stiffness. Ifthis radius is too small, however, and the strut angle at deploymentexceeds φ, there is a greater chance of yielding or other problems todevelop due to stress concentrations at the inner radius. Due to theductility and resiliency of metal, stents made from metal may also becrimped down further than shown in FIG. 7B. The struts 420, 422 maytouch each other, i.e., S is less than 2×r_(a), and yet the stent canstill recover and maintain its radial stiffness despite the over crimpedcondition.

For polymer scaffold, however, it has been found that the distance S(FIG. 7B) should not generally be smaller than allowed for the radiusr_(a), i.e., S greater than or equal to 2r_(a). For a polymer scaffold,if the struts 420, 422 are brought closer to each other, i.e., S becomesless than 2×r_(a), the brittleness of the material can likely result infracture problems when the scaffold is deployed. The scaffold may nottherefore be able to maintain its radial stiffness if crimped beyond theallowable distance for the radius. The scanning electron microscope(SEM) photographs included as FIGS. 8A, 8F and 8G show fractures atcrowns when the distance S in FIG. 7B is less than 2×r_(a). As can beseen in these photographs, there is significant material failure in a Wcrown, free crown and Y crown.

With the objective of decreasing the distance S between struts 420, 422(FIG. 7B) the inventors decided to reduce down the radius r_(a) as smallas possible, despite the advice offered by the art. It was discovered,to their surprise, that the scaffold was able to recover from thecrimped condition to the expanded condition without significant,noticeable, reoccurring or prohibitive loss in radial strength. The SEMsprovided as FIGS. 8B, 8C and 8D show crowns/valleys having reduced radiiafter being crimped, then expanded by the balloon. In these examples thecrown inner radii were made as small as the cutting tool (a green lightpico-second laser, described above) was able to produce. As can be seenby comparing FIGS. 8A, 8F and 8G with FIGS. 8B, 8C and 8D the scaffoldhaving reduced radii produced some voids but there is no crackpropagation. Structural integrity was maintained. The deployed scaffoldin these photos maintained good radial stiffness.

FIGS. 7C and 7D illustrate embodiments of a crown formation thatproduced these unexpected results. An example of a W cell having areduced radii type of crown formation just described is illustrated inFIGS. 5B and 6B. The radius r_(b) is about 0.00025 inches, whichcorresponds to the smallest radius that could be formed by the laser.The 0.00025 inch radius is not contemplated as a target radius or limiton the radius size, although it has produced the desired result for thisembodiment. Rather, it is contemplated that the radius may be as closeto zero as possible to achieve a reduced profile size. The radius,therefore, in the embodiments can be about 0.00025 (depending on thecutting tool), greater than this radius, or less than this radius topractice the invention in accordance with the disclosure, as will beappreciated by one of ordinary skill in the art. For instance, it iscontemplated that the radii may be selected to reduce down the crimpedsize as desired.

An inner radius at about zero, for purposes of the disclosure, means theminimum radius possible for the tool that forms the crown structure. Aninner radius in accordance with some embodiments means the radius thatallows the distance S to reduce to about zero, i.e., struts are adjacentand/or touch each other as shown in FIG. 7D (S′ is about, or zero).

Without wishing to be tied to a particular theory for how the scaffoldaccording to the invention is capable of being reduced down to thetheoretical minimum diameter and then expanded without loss of strength,it is believed that the selection of starting diameter being greaterthan the inflated diameter played a role in the favorable outcome. Incontrast to the previous example where a metal stent is formed from adiameter less than its inflated diameter, which smaller diameter may beselected to facilitate a smaller crimped profile, a polymer scaffoldaccording to preferred embodiments is formed from a starting diametergreater than the maximum inflated diameter for the ballooncatheter-scaffold assembly (a larger starting diameter may be preferredto reduce acute recoil, as explained below, and/or to enhance radialstrength characteristics in the deployed state as explained earlier inthe tube processing steps for the tube of FIG. 1). As such, the strutangle pre-crimp is preferably greater than the maximum crown/strut anglewhen the scaffold is deployed. Stated differently, the crown angle inFIG. 7C (pre-crimp angle) is never exceeded when the balloon expands thescaffold from the crimped to deployed state. This characteristic of thecrush recoverable polymer scaffold, i.e., pre-crimp crown angle greaterthan the deployed crown angle, is believed to provide clues as to howthe polymer scaffold in the SEM photographs was able to retain radialstrength when a minimum inner radius was used for the crown formation,contrary to the prior art. Compression, but not expansion of thescaffold when loaded by the vessel, it is believed, will not inducefurther weakening, despite the presence of voids. When the crownexperiences only a compressive deformation relative to its pre-crimpshape (FIG. 7C), the potentially weakened area near the inner radius issubjected to only compressive stresses, which do not tend to tear thecrown apart, i.e., induce crack propagation.

Crimping of the scaffold, as detailed in U.S. application Ser. No.12/861,719, includes heating the polymer material to a temperature lessthan, but near to the glass transition temperature of the polymer. Inone embodiment the temperature of the scaffold during crimping is raisedto about 5 to 10 degrees below the glass transition temperature forPLLA. When crimped to the final, crimped diameter, the crimping jaws areheld at the final crimp diameter for final dwell period. This method forcrimping a polymer scaffold having crush recovery is advantageous toreduce recoil when the crimp jaws are released. Another, unexpectedoutcome, however, was found relating to the reduced inner radius aspectof the disclosure. It was found that during the dwell period the polymerscaffold crimped profile could be reduced to a profile less than thetheoretical minimum profile.

From the example given earlier for the scaffold of FIG. 6B, the valuefor Dmin is 0.1048″ or 2.662 mm. When crimping this scaffold accordingto the crimping procedure summarized above and described in U.S.application Ser. No. 12/861,719, it was found that the scaffold could bereduced down to a crimped profile of 0.079″ or 2.0066 mm. Hence, thecrimped profile was less than Dmin for this scaffold. With this profilea protective sheath of 0.085″ OD could be placed over the scaffold. Whena drug coating was disposed over the scaffold, the profile of thescaffold with sheath was 0.092″. For this scaffold the range of radialstrength was 0.45-0.65 N/mm, range of radial stiffness was 1.00-1.20N/mm and the crush recoverability was about 90% (50% crush).

It is believed that a reduced profile less than Dmin was achieved due toa compression of the material during the dwell period. Essentially, thepressure imposed by the crimping jaws during the dwell period at theraised temperature caused the struts forming the ring to be squeezedtogether to further reduced the crimped scaffold profile. According tothese embodiments, the crimped scaffold having a profile less than itstheoretical minimum profile was successfully deployed and tested invivo. This scaffold possessed the desired radial stiffness properties,in addition to the desired crush recovery of above about 90% following a50% reduction in diameter.

In another aspect of this disclosure, the strut and crown formation fora crush recoverable polymer scaffold is formed to take the shapedepicted in FIG. 7E, for purposes of achieving a crimped profile lessthan the crimped profile for the scaffold having the crown formationshown in FIG. 7A. According to these embodiments, the crown is formedwith a radius r_(c) as shown. When this scaffold is crimped, the strutsmay be brought close together so that the distance separating them isnear zero (S″ is about, or zero). In contrast to the embodiments of FIG.7C, the radius r_(c) is made some finite or larger radii than by forminga hole or enlarged area between the ends of the struts and crown. Thethickness at the crown, t_(c)′ forming the inner radius along its innersurface may be less than the strut width (in the example of FIG. 7C andFIG. 16 the crown thickness may be larger than the strut width). Thiscan allow a larger inner radius to be used at the crown withoutincreasing the crimped profile.

In these embodiments, a scaffold having the crown formation depicted inFIGS. 7E-7F is referred to as a “key-hole” crown formation. The namewill be understood without further clarification by reference to FIG.7F, which shows a key-hole slot or opening formed by the inner wallsurfaces. In the crimped profile, the struts near the crown may bebrought closer together while a hole or opening having radius r_(c) ismore or less maintained at the crown. The distance S″ is less than twicethe radius r_(c) for the “key-hole” crown formation.

Examples of scaffold embodying patterns 300 and 200 are provided inFIGS. 6A-6B (referred to as the V2 embodiment, which has a 0.008 inchwall thickness, V23 embodiments having 0.008 and 0.014 inch wallthickness and the V59 embodiment, which has a 0.011 inch wallthickness). Specific values for the various cell attributes of FIGS.5A-5B are provided.

The scaffold V59 (pattern 200) having a pre-crimp diameter of 8 mm iscapable of being crimped to a non-compliant balloon wherein the crimpedprofile is about 2 mm. The inflated diameter is about 6.5 mm in thisexample. The scaffold V2, V23 having pre-crimp diameters 7 and 9,respectively, are expanded to about 6.5 mm by a non-compliant balloon.The V2 and V23 scaffold are capable of being crimped to diameters ofabout 0.092 inches (2.3 mm).

According to the disclosure, it was found that the aspect ratio (AR) ofa strut of a scaffold may be between about 0.8 and 1.4, the AR of a linkmay be between about 0.4 and 0.9, or the AR of both a link and a strutmay between about 0.9 and 1.1, or about 1. Aspect ratio (AR) is definedas the ratio of width to thickness. Thus for a strut having a width of0.0116 and a wall thickness of 0.011 the AR is 1.05.

According to the disclosure, the radial strength of a balloon expandedpolymer scaffold having crush recoverability has a radial strength ofgreater than about 0.3 N/mm, or between about 0.32 and 0.68 N/mm, and aradial stiffness of greater than about 0.5 N/mm or between about 0.54N/mm and 1.2 N/mm. According to the disclosure, a crush-recoverablescaffold has these ranges of stiffness and strength for a scaffoldhaving a wall thickness of about 0.008″ to 0.014″ and configured forbeing deployed by a 6.5 mm non-compliant balloon from about a 2 mmcrimped profile, or deployed to a diameter of between about 6.5 mm and 7mm from about a 2 mm crossing profile on a balloon catheter.

A biodegradable polymer, such as PLLA (and polymers generally composedof carbon, hydrogen, oxygen, and nitrogen) is radiolucent with noradiopacity. It is desirable for a scaffold to be radiopaque, orfluoroscopically visible under x-rays, so that accurate placement withinthe vessel may be facilitated by real time visualization of the scaffoldbody, preferably the end rings. A cardiologist or interventionalradiologist typically will track a delivery catheter through thepatient's vasculature and precisely place the scaffold at the site of alesion using fluoroscopy or similar x-ray visualization procedures. Fora scaffold to be fluoroscopically visible it must be more absorptive ofx-rays than the surrounding tissue. Radiopaque materials in a scaffoldmay allow for its direct visualization. One way of including thesematerials with a biodegradable polymer scaffold is by attachingradiopaque markers to structural elements of the scaffold, such as byusing techniques discussed in U.S. application Ser. No. 11/325,973.However, in contrast to other stent or scaffold, a biodegradable,bioabsorbable, bioresorbable, or bioerodable, and peripherally implantedscaffold having crush recoverability according to the disclosure hasspecial requirements not adequately addressed in the known art.

There is the unmet need of maintaining a desired stiffness property inthe vicinity of the marker-holding material (marker structure) withoutincreasing the minimum crimped diameter, e.g., Dmin. The marker-holdingmaterial must not interfere with the extremely-limited space availablefor achieving the required crossing profile or delivery diameter for thecrimped scaffold on the delivery catheter, particularly in the case of ascaffold that has a diameter reduction of 300-400% or more when crimpedfrom the starting, pre-crimp diameter to the delivery diameter, and/orwhere the target delivery diameter is about at most a theoreticalminimum diameter (Dmin) for the scaffold. It has been found that inorder to be capable of achieving a desired delivery diameter, e.g.,300-400% or more diameter reduction during crimping, the marker material(when located on a link) should not interfere with the folding of thestruts forming rings of the scaffold. However, when addressing this needwithout consideration for the effect on radial stiffness, it was foundthat there was an unacceptable loss in stiffness in the vicinity of themarker structure.

Referring to FIGS. 9A and 9B there are shown portions of the scaffoldaccording to pattern 200. FIG. 9A shows the portion of the scaffoldwhere the link 237 holding a radiopaque material 500 (marker 500) islocated. FIG. 9B shows this same portion of the scaffold when configuredin a crimped configuration. The rings 212 b, 212 c, 212 d and 212 f areshown in their compressed, folded or compact configuration as crimpedrings 212 b′, 212 c′, 212 d′ and 212 f′, respectively. So that each ofthe rings 212 may have the same radial stiffness properties (ignoringlink connections), the pair of markers 500 is preferably located on thelink 237, as opposed to on a ring strut 230. In other embodiments themarker 500 may be located on the ring 212 by making suitableaccommodation in the ring structure.

As can be appreciated from FIG. 9B, in order to maintain the minimumdiameter, e.g., about at least the theoretical minimum crimped diameter(Dmin) for the crimped scaffold, the presence of marker structurepreferably has no effect on the distance between folded struts 230. Toachieve this result, the length of the link 237 may be increased,(L₂₃₇=L₁+L₂), over the length L₁ of the other links 234 that do not havethe markers to carry (the length L₂ being about the length needed toaccommodate marker structure (depots 502 and the pair of markers 500),without interfering or limiting the folding of struts 230 as necessaryto achieve a 300-400% or more diameter reduction. Stents or scaffoldthat do not have a tight crimped diameter requirement or minimum spacebetween structural elements of a scaffold, by contrast, may have thelink connecting rings increased in size beneath the fold struts to holda marker 500, since there remains available space for marker structurein the crimped configuration.

The depots 502 may be formed when the scaffold is cut from the tube. Thedepots 502 provide a hole sized slightly smaller than a diameter of amarker 500 sphere, e.g., a platinum sphere, so that the sphere may beplaced in the hole and secured therein as a drug-polymer coating isapplied over the scaffold. The drug-polymer coating can serve as anadhesive or barrier retaining the marker 500 within the hole of a depot502.

In one aspect of the disclosure the diameter of a sphere forming themarker 500 necessary to achieve adequate illumination is less than thewall thickness (235, FIG. 3) of the polymer scaffold. As such, thesphere may be placed within the hole and then a coating applied over it.Since the sphere diameter is about equal to or less than the wallthickness 235 no reforming, or shaping of the sphere is necessary toachieve a flat profile. A process of applying the marker, therefore, issimplified.

When the length of a link having marker structure is increased tomaintain the minimum crimped diameter according to the embodiments ofFIG. 9, however, the combined radial stiffness properties of the nearbyrings is reduced since they are spaced further apart. To minimize thisloss in stiffness, particularly with respect to the end ring (which isinherently less stiff since it is connected to only one neighboringring), the marker structure is located between links 212 c and 212 f, asopposed to rings 212 d and 212 f. Additionally, the marker structure isarranged so that the marker pair 500 is placed in depots 502 a, 502 borientated along the vertical axis B-B as opposed to longitudinally(axis A-A). By placing the depots 502 a and 502 b along axis B-B thelength L₂ is preferably less than if the markers 500 were disposedlongitudinally, so that the undesirable loss in the combined radialstiffness of the adjacent rings 212 c, 212 f (resulting from theincreased length of link 237) and the end ring 212 d is minimal.

According to another embodiment of a marker for the polymer scaffold, ascaffold according to the pattern 200 may be devoid of link 237 havingthe marker structure and increased length needed to accommodate crimpingrequirements. Referring to FIGS. 10A and 10B, instead, a radiopaquesheet of material 504, e.g., a 0.025″ length and 0.004″ thick gold,platinum or Iridium foil, is wrapped around a link 234 and held in placeby, e.g., a drug-polymer coating deposited over the scaffold. Since thethickness of the foil may be negligible, or the material compressibleduring crimping, the scaffold may be capable of maintaining at leastabout a Dmin crimped diameter despite the presence of the marker 504between folded struts 230. According to these embodiments, since thefoil does not affect scaffold function—the link length may be about thesame as other links 234—the foil may be preferably placed nearer to theend of the scaffold to facilitate easier identification of the scaffoldend within the vessel. For example, the marker 504 may be located on thelink connecting ring 212 d to ring 212 f since stiffness properties arenot affected by the presence of the marker 504.

According to other embodiments of a marker for the polymer scaffold, asdepicted in FIGS. 11A and 11E, a scaffold according to the pattern 200is modified in the ring structure to hold a radiopaque marker. Byplacing marker(s) material on or near a crown 207 of the end ring 212 d,as shown in FIGS. 11A-11E, the location of the end ring 212 d in thevessel can be more easily located (since the marker is located on theend ring). According to the embodiments depicted in FIGS. 11A, 11B and11E one or more cylindrically shaped markers 511, 516, 531,respectively, may be located at the crown 207 (FIGS. 11A and 11B) ornear the crown 207 as in FIG. 11E. According to the embodiments depictedin FIGS. 11C and 11D one or more strips of radiopaque material 521, 526are placed near the crown (FIG. 11C) or around the crown (FIG. 11D).

A single marker 511 may be received in a hole 512 formed at the crown207, in the case of FIG. 11A, or received in a hole provided by aneyelet 519 that extends from the crown 207, as shown in FIG. 11B. In thelater case, it may be necessary to increase the ductility, or fracturetoughness of the material forming the extension 519 to avoid the eyeletbreaking off from the crown 207. Since there is no strength/stiffnessrequirements for this eyelet, it may be practical to alter the materiallocally so that it is more fracture resistant without affecting thestiffness of the crown. For example, Toughness could be achieved bylocal heat treatment, local plasticization, or a local coatingapplication. Local heat treatment could be particularly useful if apolymer blend or a block copolymer is used in the backbone of thescaffold. FIG. 11E shows three radiopaque pieces 531 received in threeholes formed in the strut 532, which has been made thicker toaccommodate for the loss in strength of the strut 230 due to thepresence of the holes 534.

FIGS. 11C and 11D show examples of a strip of radiopaque material 521,526 received in slots 522, 528, respectively, formed in the ring 212 b.The strip 521 may be located in the strut 524, or the strip 526 may belocated about the crown 207 to increase visibility of the crown. Thesedesign choices should also take into account the affect on the bendingstiffness of this crown, which is also true of the embodiment of FIG.11A. Preferably the slot 522, 528 coincides with the neutral axis of thestrut and/crown to minimize the effect on bending stiffness at thecrown.

In other embodiments the strips 521, 526 may be made from a materialconsisting of radiopaque particles dispersed in a bioresorbablematerial, e.g., 60% Tungsten particles. This embodiment has theadvantage of dispersing the radiopaque material within the vessel afterthe scaffold has biodegraded.

In another embodiment a scaffold may have links connecting the end ringslengthened to accommodate a marker, e.g., as shown in FIG. 9A-9B,without losing substantial radial strength or stiffness at the end ring(due to the increased length of the link) by having metallic springelements inserted into the crowns. Thus, according to this embodimentthere is a marker element.

In another embodiment a metallic or composite metal-polymer spring mayserve a dual role of providing greater visibility and strengthening theend ring. Referring to FIG. 11F there is shown a modified form of thenon-symmetric cell 304′ when the end ring 312 b′ forms one of its sides.At the free crown 307, Y-crown 309 and W crown 310 there is an archedstrengthening element, or spring 460 embedded in the crown. The materialfor member 460 may be, or may include, e.g., Iron, Magnesium, Tungstento provide, in addition to added strength/stiffness at the crown,greater visibility of the end of the scaffold when implanted within thebody as these materials are radiopaque. The positioning of the member460 relative to a strut's neutral axis may be closest to its edge suchas nearest the outer end of the crown, e.g., furthest from the innerradius of the crown so that the tensile ultimate stress across the strutwhen the ring is under compression is increased mostly due to thepresence of the member 460. The member 460 is preferably located at eachof the crowns at the end ring to serve a dual role of providing greatervisibility and adding additional radial strength and stiffness to theend ring (which would otherwise have less radial stiff than interiorring structure since the end ring is connected to only one neighboringring).

Design Process

As mentioned earlier, the problem may be stated in general terms asachieving the right balance among three competing design drivers: radialstrength/stiffness verses toughness, in-vivo performance versescompactness for delivery to a vessel site, and crush recovery versesradial strength/stiffness.

Embodiments having patterns 200 or 300 were found to produce desiredresults with particular combinations of parameters disclosed herein, orreadily reproducible in light of the disclosure. It will be recognizedthere were no known predecessor balloon-expandable stents havingadequate crush recovery to use as a guide (indeed, the art haddiscouraged such a path of development for a peripheral stent). As such,various polymer scaffold combinations were fabricated based and thefollowing properties evaluated to understand the relationships bestsuited to achieve the following objectives:

Crush recoverability of the scaffold without sacrificing a desiredminimal radial stiffness and strength, recoil, deploy-ability andcrimping profile;

Acute recoil at deployment—the amount of diameter reduction within ½hour of deployment by the balloon;

Delivery/deployed profile—i.e., the amount the scaffold could be reducedin size during crimping while maintaining structural integrity;

In vitro radial yield strength and radial stiffness;

Crack formation/propagation/fracture when crimped and expanded by theballoon, or when implanted within a vessel and subjected to acombination of bending, axial crush and radial compressive loads;

Uniformity of deployment of scaffold rings when expanded by the balloon;and

Pinching/crushing stiffness.

These topics have been discussed earlier. The following providesadditional examples and conclusions on the behavior of a scaffoldaccording to the disclosure, so as to gain additional insight intoaspects of the disclosed embodiments.

A scaffold fabricated with a pattern similar to pattern 300 (FIG. 4)possessed a good amount of crush recoverability, however, thisscaffold's other properties were not ideal due to memory in the materialfollowing balloon expansion. The scaffold, which was initially formedfrom a 6.5 mm tube and deployed to about the same diameter, had acuterecoil problems—after deployment to 6.5 mm it recoiled to about a 5.8 mmdiameter. The scaffold also exhibited problems during deployment, suchas irregular expansion of scaffold rings.

One attempt at solving the design problem proceeded in the followingmanner. The scaffold's properties were altered to address stiffness,strength, structural integrity, deployment and recoil problems whilemaintaining the desired crush recoverability. Ultimately, a scaffold wasdesigned (in accordance with the disclosure) having the desired set ofscaffold properties while maintaining good crush recovery propertiesafter a 50% pinch deformation, which refers to the scaffold's ability torecover its outer diameter sufficiently, e.g., to about 90-95%,following a crushing load that depresses the scaffold to a height aboutequal to 50% of its un-deformed height.

The pinching stiffness (as opposed to the radial stiffness) is mostinfluenced or most sensitive to changes in the wall thickness of thescaffold. As the wall thickness increases, the pinching stiffnessincreases. Moreover, the crush recoverability of a scaffold is mostaffected by the stresses created at the regions that deflect mostoutward in response to the applied load. As explained below, as the wallthickness is increased, the crush recoverability decreases due to anincreased concentration of strain energy at the outwardly deflected endsof the scaffold. A design for a crush recoverable scaffold, therefore,must balance the wall thickness for increased pinching stiffness againstthe reduction in crush recoverability resulting from an increasedpinching stiffness. Similarly, although radial stiffness is lessaffected by changes in wall thickness (since loads are morepredominantly in-plane loading as opposed to out of plane duringpinching) when wall thickness is altered to affect crush recoverabilitythe radial stiffness must be taken into consideration. Radial stiffnesschanges when the wall thickness changes.

The diagrams drawn in FIGS. 12A, 12B and 12C are offered to assist withexplaining a relationship between wall thicknesses and crushrecoverability. FIG. 12A shows a cross-section of a scaffold in itsun-deformed (unloaded) state and deformed state when subjected to apinching load (drawn in phantom). The ends of the scaffold designated by“S” and “S′” refer to regions with the highest strain energy, as one canappreciate by the high degree of curvature in these areas when thescaffold is under the pinching load. If the scaffold will not recover orhave reduction in recovery from the pinching load (F), it will bebecause in these regions the material has yielded, which precludes orreduces recovery back to the pre-crush diameter. The equal and oppositecrushing forces in force F in FIG. 12A deflect the scaffold height fromits un-deformed height, i.e., the scaffold diameter, to a deformedheight as indicated by δ. The region of the scaffold that will containthe highest degree of strain energy when the crushing force F is beingapplied is near the axis of symmetry for the deformed shape, which isshown in phantom. In the following discussion, the load reaction ormaterial stress/strain state at the scaffold regions S and S′ will beexpressed in terms of the strain energy.

FIGS. 12B and 12C are simplified models of the loaded structure intendedto illustrate the effects on the strain energy in region S when thescaffold has different wall thickness. Essentially, the model attemptsto exploit the symmetry of the deformed shape in FIG. 12A to construct alinear stress-strain representation at region S in terms of a springhave a spring constant K. Accordingly, the scaffold properties aremodeled as arcs 10/20 (½ of a hoop or ring) or half-cylinder shellssupported at the ends. The arc cannot displace downward (Y-direction)when the enforced displacement δ is applied, which is believedacceptable as a boundary condition due to the symmetry in FIG. 12A.Movement in the x-direction is restrained by the spring having springconstant K. The hemispherical arc 10 in FIG. 12C has a thickness t₁ andthe hemispherical arc 20 in FIG. 12B has a thickness of t₂>>t₁.

As the pinching load is applied in FIGS. 12B and 12C, the arcs 10 and 20are deformed (as shown in phantom). This is modeled by an enforceddisplacement of the arcs 10/20 at their center by about the amount delta(δ) as in FIG. 12A. The arc 10 deforms less than arc 20, however, interms of its curvature when the enforced displacement is applied,because its flexural rigidity is higher than arc 20. Since the curvatureis less changed in arc 10, more of the % strain energy resulting fromthe enforced displacement will be carried by the spring at the ends,where the spring force is restraining outward movement at S. For arc 20more % strain energy is carried in the arc, as the greater changes ofcurvature are intended to show, as opposed to the spring restrainingmovement at the ends.

Consequently, for a given applied force the % strain energy at the endswill be greater for arc 10, since the flexural rigidity of the arc 10 isgreater than the arc 20. This is depicted by the displacement of thespring (x₂>x₁). The % strain energy in the spring restraining arc 20(i.e., ½ K(x₂)²/(total strain energy in arc 20)×100) is greater than the% strain energy in the arc 10 restraining spring (i.e., ½ K(x₁)²/(totalstrain energy in arc 10)×100). From this example, therefore, one cangain a basic appreciation for the relationship between wall thicknessesand crush recoverability.

In a preferred embodiment it was found that for a 9 mm scaffoldpre-crimp diameter a wall thickness of between 0.008″ and 0.014″, ormore narrowly 0.008″ and 0.011″ provided the desired pinching stiffnesswhile retaining 50% crush recoverability. More generally, it was foundthat a ratio of pre-crimp (or tube) diameter to wall thickness ofbetween about 30 and 60, or between about 20 and 45 provided 50% crushrecoverability while exhibiting a satisfactory pinching stiffness andradial stiffness. And in some embodiments it was found that a ratio ofinflated diameter to wall thickness of between about 25 and 50, orbetween about 20 and 35 provided 50% crush recoverability whileexhibiting a satisfactory pinching stiffness and radial stiffness.

Wall thickness increases for increasing pinching stiffness may also belimited to maintain the desired crimped profile. As the wall thicknessis increased, the minimum profile of the crimped scaffold can increase.It was found, therefore, that a wall thickness may be limited both bythe adverse effects it can have on crush recoverability, as justexplained, as well as an undesired increase in crimped profile.

Testing

Provided below are results from various tests conducted on scaffolds andstents for purposes of measuring different mechanical properties andmaking comparisons between the properties of the stents and scaffolds.The stents used in the tests were the Cordis® S.M.A.R.T.® CONTROL® Iliacself-expanding stent (8×40 mm) (“Control stent”), the REMEDY Stent (6×40mm) by Igaki-Tamai (“Igaki-Tamai stent”), and the Omnilink Elite® stent(6×40 mm).

The data presented in Tables 2-6 for the scaffolds V2, V23 and V59 arefor scaffolds having the properties listed in Tables 6A and 6B,respectively. The scaffolds were crimped to a delivery balloon, thenexpanded to their inflated diameter using a process similar to theprocess described at paragraphs [0071]-[0091] of U.S. application Ser.No. 12/861,719.

The data presented in Tables 2-6 refer to scaffolds and stent propertiesafter they were expanded by their delivery balloons. For each of thetests reported in Tables 2-6, infra, unless stated otherwise thestatistic is a mean value.

Table 2 presents data showing the percentage of crush recovery forvarious scaffold compared with other types of stents. The scaffolds andstents were crushed using a pair of opposed flat metal plates movedtogether to crush or pinch the stents and scaffold by the respectiveamounts shown in the tables. The test was conducted at 20 degreesCelsius.

Table 2 compares the crush-recoverability of the V2, V23 and V59scaffold to the Igaki-Tamai stent and Omnilink Elite® (6 mm outerdiameter and 40 mm length) balloon expandable stent. The crush periodwas brief (about 0 seconds).

TABLE 2 Approximate crush recovery using flat plate test at 20 Deg.Celsius (as percentage of starting diameter, measured 12 hours followingcrush) when when when when crushed to crushed to crushed to crushed to18% of 33% of 50% of 65% of Stent/scaffold starting starting startingstarting type diameter diameter diameter diameter V23 (.008″ wall 99%96% 89% 79% thickness) V23 (.014″ wall 99% 93% 84% 73% thickness) V59(.011″ wall 99% 96% 88% 80% thickness) Igaki-Tamai 99% 94% 88% 79%Omnilink Elite^((R)) 93% 80% 65% 49%

As can be seen in the results there is a dramatic difference between theV2, V23 and V59 crush recovery compared with the Omnilink Elite®coronary stent. The best results are achieved by the V23 (0.008″ wallthickness) and V59 scaffold when taking into consideration the radialstrength and stiffness properties of these scaffold compared with theIgaki-Tamai stent (see Table 5).

Table 3 compares the crush recovery behavior for a V23 scaffold with0.008″ wall thickness (FIG. 6A) following a 50% crush. The data showsthe percent crush recovery of the V23 scaffold following a brief(approximately 0 seconds), 1 minute and 5 minute crush at 50% of thestarting diameter.

TABLE 3 Approximate crush recovery of V23 (.008″ wall thickness) usingflat plate test at 20 Deg. Celsius (as percentage of starting diameter,measured 24 hours following crush) when crushed to 25% of when crushedto 50% Crush duration starting diameter of starting diameter 0 secondcrush 100% 99% 1 minute crush 99% 86% 5 minute crush 92% 83%

FIG. 13 shows the crush recovery properties for the V59 scaffold whencrushed to 50% of its starting diameter over a 24 hour period followingremoval of the flat plates. There are three plots shown corresponding tothe recovery of the scaffold following a 0 second, 1 minute and 5 minutecrush duration. The scaffold diameter was measured at different timepoints up to 24 hours after the flat plates were withdrawn. As can beseen in these plots, most of the recovery occurs within about 5 minutesafter the flat plates are withdrawn. It is contemplated, therefore, thatan about 90% crush recovery is possible for longer periods of crush,e.g., 10 minutes, ½ hour or one hour, for scaffold constructed accordingto the disclosure.

When the pinching or crushing force is applied for only a brief period(as indicated by “0 sec hold time (50%)” in FIG. 13) tests indicate arecovery to about 95-99% of its initial diameter. When the force is heldfor 1 minute or 5 minute, tests indicate the recoverability is less. Inthe example of FIG. 13, it was found that the scaffold recovered toabout 90% of its initial diameter. The 1 minute and 5 minute timeperiods being about the same suggests that any effects of thevisco-elastic material succumbing to a plastic or irrecoverable strainwhen in a loaded state has mostly occurred.

In accordance with the disclosure, a crush-recoverable polymer scaffold(having adequate strength and stiffness properties, e.g., the stiffnessand strength properties of the scaffold in Table 4, infra) has a greaterthan about 90% crush recoverability when crushed to about 33% of itsstarting diameter, and a greater than about 80% crush recoverabilitywhen crushed to about 50% of its starting diameter following anincidental crushing event (e.g., less than one minute); acrush-recoverable polymer scaffold has a greater than about 90% crushrecoverability when crushed to about 25% of its starting diameter, and agreater than about 80% crush recoverability when crushed to about 50% ofits starting diameter for longer duration crush periods (e.g., betweenabout 1 minute and five minutes, or longer than about 5 minutes).

An acute recoil problem was observed. In one example, a scaffold wasformed from a 7 mm deformed tube having a 0.008″ wall thickness. Whenthe scaffold was balloon deployed to 6.5 mm, the scaffold recoiled toabout 5.8 mm. To address this problem, the scaffold was formed fromlarger tubes of 8 mm, 9 mm and 10 mm. It was found that a largerpre-crimp diameter relative to the intended inflated diameter exhibitedmuch less recoil when deployed to 6.5 mm. It is believed that the memoryof the material, formed when the deformed tube was made, reduced theacute recoil.

A starting tube diameter of 10 mm, for example, for a scaffold having a7.4 mm inflated diameter should exhibit less recoil than, say, a 8 mmtube, however, this larger diameter size introduced other problems whichdiscouraged the use of a larger tube size. Due to the larger diameter itbecame difficult, if not infeasible to reduce the diameter duringcrimping to the desired crimped diameter of about 2 mm. Since there ismore material and a greater diameter reduction, there is less spaceavailable to reduce the diameter. As such, when the starting diameterexceeds a threshold, it becomes infeasible to maintain the desiredcrimped profile. It was found that a 9 mm tube size produced acceptableresults in that there was less recoil and a crimped profile of about 2mm could still be obtained.

An excessive starting diameter can introduce other problems duringdeployment. First, when the diameter reduction from starting diameter tocrimped diameter is too great, the local stresses in the scaffold hingeelements, crowns or troughs correspondingly increase. Since the polymermaterial tends to be brittle, the concern is with cracking or fractureof struts if stress levels are excessive. It was found that the diameter9 mm starting diameter scaffold (in combination with other scaffolddimensions) could be reduced down to 2 mm then expanded to the 7.4 mminflated diameter without excessive cracking or fracture.

Table 4 compares the acute recoil observed in the V2, V23 and V59scaffold of FIGS. 6A and 6B.

TABLE 4 Acute recoil comparisons Stent/scaffold type percent recoil V2(.008″ wall thickness) 11.3% V23 (.008″ wall thickness) 3.9% V23 (.014″wall thickness) 4.3% V59 (.011″ wall thickness) 4.5%

As discussed earlier, unlike a metal stent, a design for a polymerscaffold must take into consideration its fracture toughness both duringcrimping and when implanted within a vessel. For a scaffold locatedwithin a peripheral artery the types of loading encountered are ingeneral more severe in terms of bending and axial loading than acoronary scaffold, in addition to the pinching or crush forcesexperienced by the scaffold, due to the scaffold's proximity to thesurface of the skin, and/or its location within or near an appendage ofthe body. See e.g. Nikanorov, Alexander, M. D. et al., Assessment ofself-expanding Nitinol stent deformation after chronic implantation intothe superficial femoral artery.

As is known in the art, a scaffold designed to have increased radialstiffness and strength properties does not, generally speaking, alsoexhibit the fracture toughness needed for maintaining structuralintegrity. The need to have a peripherally implanted polymer scaffoldwith adequate fracture toughness refers both to the need to sustainrelatively high degrees of strain in or between struts and links of thescaffold and to sustain repeated, cyclical loading events over a periodof time, which refers to fatigue failure.

The methods of manufacture, discussed earlier, of the tube from whichthe scaffold is formed are intended to increase the inherent fracturetoughness of the scaffold material. Additional measures may, however, beemployed to reduce instances of fracture or crack propagation within thescaffold by reducing the stiffness of the scaffold in the links, or byadding additional hinge points or crown elements to the ring.Alternatively or in addition, pre-designated fracture points can beformed into the scaffold to prevent fracture or cracks from propagatingin the more critical areas of the scaffold. Examples are provided.

As mentioned above, a peripherally implanted polymer scaffold issubjected, generally speaking, to a combination of radial compressive,pinching or crushing, bending and axial compression loads. Test resultsindicate that a majority of cracks can occur in the struts forming aring, as opposed to the links connecting rings for a peripherallyimplanted polymer scaffold. Indeed, while bench data may suggest that ascaffold is quite capable of surviving cyclical radial, bending andaxial loadings when implanted in a peripheral vessel, when the scaffoldis in-vivo subjected to combined axial, flexural and radial loading in aperipheral vessel there is nonetheless unacceptable crack formation,fracture or significant weakening in radial strength.

With this in mind, alternative embodiments of a scaffold pattern seek toweaken, or make more flexible the scaffold in bending and axialcompression without significantly affecting the radial strength orstiffness of the scaffold. By making links connecting rings moreflexible, relative movement between a ring and its neighbor, whichoccurs when a scaffold is placed in bending or axial compression whenrings are not axially aligned with each other, e.g., when the scaffoldresides in a curved vessel, does not produce as a high a loading betweenthe ring and its neighbor since the link tends to deflect more inresponse to the relative movement between the rings, rather thantransfer the load directly from one ring to another.

Referring to an alternative embodiment of pattern 200, a scaffold isconstructed according to the pattern depicted in FIGS. 14A and 14B.Pattern 400 is similar to pattern 200 except that a link 434/440connecting the rings 212 is modified to create greater flexibility inthe scaffold in bending and axial compression (or tension). Referring toFIG. 14B, the link 434 includes a first portion 435 having a firstmoment of inertia in bending (MOI₁) nearest a Y-crown of a ring and asecond portion 438 having a second moment of inertia (MOI₂) in bendingnearest a W-crown of the neighboring ring, where MOI₁<MOI₂.Additionally, a U-shaped portion 436 is formed in the portion 435 tocreate, in effect, a hinge or articulation point to reduce bendingstiffness further. The U-shape portion 436 opens when the ring 212rotates clockwise in FIG. 14B. As such, the link is very flexible inclockwise bending since the bending stiffness about the hinge 436 a isvery low. For counterclockwise rotation, the ends of the U-shapedportion abut, which in effect negates the effect of the hinge 436 a.

To construct a scaffold that is equally flexible for both clockwise andcounterclockwise bending of the scaffold, the U-shaped portions 434 maybe removed so that the increased flexibility is provided solely by thereduced MOI portions of the links, such as by replacing the U-shapedportion 436 in FIG. 14B with a straight section having a reduced MOI. Analternative is depicted in FIG. 14A, which shows alternating invertedU-Links 440 b and U-links 440 a. When the scaffold is subject to aclockwise bending moment (i.e., ring 212 d is displaced downwardly inFIG. 14A relative to ring 212 e) the U-shaped portions of the U-links440 a act as hinge points. The “U” opens in response to the relativemovement between the adjacent rings 212, whereas the inverted U-links440 b function, essentially, as straight sections since the ends of theinverted “U” will contact each other. Similarly, when the scaffold issubject to a counterclockwise bending moment (i.e., ring 212 d isdisplaced upwardly in FIG. 14A relative to ring 212 e) the invertedU-shaped portions of the inverted U-links 440 b act as hinge points. Theinverted “U” opens in response to the relative movement between theadjacent rings 212, whereas the U-links 440 a function, essentially, asstraight sections since the ends of the “U” each other when the scaffolddeflects.

In another embodiment a reduced MOI may be achieved by increasing thedistance between each ring, or preferably every other ring. For example,the distance between ring 212 a and 212 b in FIG. 2 may be increased(while the distance between rings 212 c, 212 b remains the same). Inthis example, a link connecting rings 212 a and 212 b can have the sameMOI as the link connecting rings 212 b and 212 c yet the former linkwill be less stiff in bending since its length is longer than the laterlink.

In another alternative, the pattern 400 includes a link 442 withopposing “U” shaped portions or an “S” portion, as depicted in FIG. 14C.The S-link 442 has the MOI₁ and MOI₂ as before, except that the portion435 of the link 442 has two hinge points, 444 a and 444 b, instead ofthe one in FIG. 14B. With this arrangement, the link 442 provides ahinge point to increase bending flexibility for both clockwise andcounterclockwise bending. As such, for a pattern 400 having links 442the same link 442 may be used everywhere to achieve greater bendingflexibility for both clockwise and counterclockwise bending.

FIGS. 14D through 14F illustrate additional embodiments of a link 442extending between and connecting the Y and W crowns. These examples showlinks having variable MOIs, either by shaping the link as the pattern iscut from a tube or by modifying the link after the scaffold has been cutfrom the tube.

FIGS. 14D and 14F show links 450 and 454, respectively, formed to have asection having a lower MOI than sections located adjacent the connectingcrowns. In the case of link 450 the section 451 having the low MOI isoffset from, or non-symmetric about the neutral axis “X” in bending forthe sections adjacent crowns. In the case of link 454 the section 455 issymmetric about the neutral axis for the sections adjacent the crowns.This symmetry/non-symmetry contrast for sections 451 and 452 may also bedescribed with respect to an axis of symmetry for the crowns. Thus, foran axis of symmetry “X” for a Y-crown (210) or W crown (209), which canbe readily identified from the figures, section 451 is asymmetric aboutthe X axis, whereas the necked section 455 of the link 454 is symmetricabout this axis, which may be considered a crown axis.

FIG. 14E illustrates an example where material between the ends of thelinks are removed to form two curved voids 433 a, 433 b in the link 452.These embodiments may function in a similar manner as the “S” linkdiscussed earlier. According to this embodiment, a pre-designatedfracture point (to fail before the rings fail) is between the voids 433a, 433 b. The material forming the voids 433 a, 433 b may be about thesame so as to retain symmetry about the axis X, or they may be adifferent size to cause the axis of symmetry to not be co-linear withthis axis, as in the case of FIG. 14D. The selection of the void size isbased on the desired fracture characteristics relative to the ring andwhether it is preferred to have a link less stiff for bending in theclockwise or counterclockwise direction, as explained earlier.

In another embodiment, greater fatigue and/or fracture toughness may beachieved by modifying the struts of the ring. Referring to FIG. 15,there is shown a pattern similar to pattern 300 except that the rings450 are formed by curved struts 452 connected at crowns 451. In thisexample the struts 452 have a shape approximating one sinusoidal period.By replacing the straight struts of FIG. 4 with sinusoidal struts thereis essentially additional hinge points created in the ring.

The number of modified link elements, as discussed in connection withFIGS. 14A-14C may be between 5-100% of the links used to connect ringsof the scaffold. The U-links or S-links as described may be placedbetween each ring, or may be placed between every-other ring pair.Additionally, the links may be modified by having their MOI reducedwithout U or S links. Additionally, one or more connecting links can beremoved. When there are less connecting links, e.g., 3 verses 4, thescaffold should generally have a reduced bending and axial stiffness(assuming everything else in the scaffold is unchanged). However, asmentioned earlier, the end-to-end or overall effects on performance,reproducibility, quality control and production capacity for such changein a scaffold is, unfortunately, not as easy to predict as in the caseof a metal stent.

In another aspect of the disclosure, there is a scaffold pattern havingrings formed by closed cells. Each of the closed cells of a ring share alink element that connects the longitudinally-spaced andcircumferentially extending strut portions of the closed cell. Each ofthese closed cell rings are interconnected by a connecting link e.g.,links, 434, 442, 450, 452 or 454, having a reduced bending moment ofinertia (MOI) to reduce the flexural rigidity of the structureconnecting the closed cell rings. Alternatively, the connecting link caninclude a pre-designated fracture point, such as by forming an abruptchange in geometry near a high strain region. Returning again to FIG.14A, the scaffold pattern depicted has links 440 a connected to eachclosed cell ring. For each closed cell 204 there is a first and secondconnecting link, which are co-linear with each other. The first link hasa MOI₁ disposed adjacent the crown and the second link has a MOI₂disposed distal the crown to produce the pattern shown in FIG. 14A.Alternatively the links connecting the closed cell rings may have theMOI₁ disposed equidistant from the interconnected closed cell rings.

According to an additional aspect of the disclosure, there is a scaffoldthat includes pre-designated fracture points in the links connectingrings. The fracture points are intended to relive the inter-ring loadingthrough crack formation in the links connecting rings. Since the loadingon a crown is reduced or eliminated when there is sufficient crackpropagation through the link (load cannot transfer across a crack), byincluding a pre-designated crack location, one may maintain theintegrity of the ring structure at the expense of the links, e.g., links450, 452, in the event in-vivo loading exceeds the design, particularlywith respect to fatigue loading. According to this aspect of thedisclosure a link has a reduced MOI near a high strain region andincludes an abrupt geometry change, e.g., about 90 degrees mid-span.These pre-designated fracture point in the scaffold may extend betweenclosed cell rings, as described above, or between each ring strut.

Cracking/fracture problems are also observed as a consequence ofirregular crimping and/or deployment of the scaffold. Irregulardeployment is problematic, not only from the viewpoint of the scaffoldnot being able to provide a uniform radial support for a vessel, butalso from the viewpoint of crack propagation, fracture and yielding ofstructure resulting in loss of strength and/or stiffness in vivo.Examples of irregular deployment include crowns being expanded beyondtheir design angles and in extreme cases, flipping or buckling of crownsduring deployment or crimping. These problems were observed duringcrimping process and during deployment, examples of which are describedin greater detail in U.S. application Ser. No. 12/861,719.

Pattern 300 may be susceptible to more of these types of problems thanpattern 200. The links of the pattern provide less support for the ringstruts forming the V segment of the W-V closed cell 304, as compared topattern 200. It is believed that the w-shaped closed cell 204 was morecapable of deploying without irregularities, such as flipping, due toits symmetry. The asymmetric loading inherent in the W-V cell 304 wasmore susceptible to buckling problems during crimping or deployment.These potential problems, however, should they arise, may be addressedby adopting modifications to the crimping process.

For example, a scaffold having a diameter of 7 mm and asymmetric closedcells (pattern 300) was crimped then deployed without any flipping ofstruts observed. A second scaffold of 9 mm diameter was then crimped toa balloon and deployed. This scaffold had the same pattern 300 as the 7mm scaffold. The strut or crown angle was increased by the ratio of thediameters, i.e., increased by a factor of 9/7, to compensate for thechange in radial stiffness resulting from the increased diameter. Whenthe 9 mm scaffold was crimped, however, flipping occurred in thescaffold struts (primarily in the V section of the W-V closed cell). Tocorrect this problem the W closed cell (pattern 200) was tested. Thismodification helped to reduce instances of flipped struts. Surprisingly,the same irregular crimping/deployment problems have not been observedfor the comparable metal stent having a W-V closed cell pattern. It wasconcluded, therefore, that the flipping problem (in particular) is aphenomenon unique to a polymer scaffold.

To avoid flipping phenomena, should it occur in a metal stent, one mightconsider simply adjusting the moment of inertia of a strut to preventout of plane (outside of the arcuate, abluminal surface) deflection of astrut. However, as noted earlier, the polymer material introducesconstraints or limitations that are not present with a metallicmaterial. In the case of minimizing undesired motion of a strut bymodifying bending inertia properties of the strut one needs to bemindful that polymer struts must, generally speaking, be thicker and/orwider than the equivalent metal strut. This means there is less spaceavailable between adjacent struts and already higher wall thicknessesthan the metal counterpart. This problem of space is further compoundedfor embodiments that form a polymer scaffold from a tube that is thedeployed, or larger than deployed size. It is desirable to have thescaffold reduced in diameter during crimping for passage to the samevessel sites as in the case of the metal stent. Thus, the deliveryprofile for the crimped scaffold should be about the same as the metalstent.

A metal stent may be cut from a tube that is between the deployed andcrimped diameters. As such, the spacing between struts is greater andthe stent is more easily compressed on the balloon because the stentpre-crimp has a diameter closer to the crimped diameter. A polymerscaffold, in contrast, may be cut from a diameter tube equal to orgreater than the deployed state. This means there is more volume ofmaterial that must be packed into the delivery profile for a polymerscaffold. A polymer scaffold, therefore, has more restraints imposed onit, driven by the crimped profile and starting tube diameter, thatlimits design options on strut width or thickness.

A well known design requirement for a vessel supporting prosthesis,whether a stent or scaffold, is its ability to maintain a desired lumendiameter due to the inward radial forces of the lumen walls includingthe expected in vivo radial forces imparted by contractions of the bloodvessel. Referring to the examples in FIGS. 6A-6B, the radial stiffnessand radial strength of the scaffold is influenced by the width ofstruts, crown radii and angles, length of ring struts extending betweencrowns and valleys, the number of crowns and the wall thickness(thickness 235, FIG. 3) of the scaffold. The latter parameter (wallthickness) influences the pinching stiffness, as explained earlier.During the design process, therefore, this parameter was altered toaffect pinching stiffness and crush recoverability, although it also hasan effect on radial stiffness. In order to affect the radial stiffness,one or more of the foregoing parameters (crown angle, crown radius, ringstrut length, crown number, and strut width) may be varied to increaseor decrease the radial stiffness.

To take one example, when it was found that a 7 mm scaffold's recoilproblem could be overcome by increasing the starting tube diameter to 8mm, 9 mm or perhaps even 10 mm, an initial approximation to thecorresponding changes to the scaffold pattern dimensions involvedincreasing characteristics such as ring strut length, crown angle andlink by the ratio of the diameters, e.g., 8/7 when increasing OD from 7mm to 8 mm. However, this rough approximation was found to beinsufficient in retaining other desired properties, such as crushrecoverability. Thus, further refinements were needed.

The relationships between radial stiffness and above mentionedparameters are well known. However, the relationship of thesestiffness-altering parameters to crush recoverability of a balloonexpandable stent, much less a balloon expandable scaffold is not wellknown, if known at all in the existing art. Accordingly, the designprocess required the constant comparison or evaluation among radialstiffness, pinching stiffness and crush recoverability (assuming thechanges did not also introduce yield or fracture problems duringcrimping and deployment) when the stiffness parameters were altered todetermine whether these and related scaffold properties could beimproved upon without significant adverse effects to crushrecoverability.

When varying these parameters to affect stiffness the followingobservations were made for a 9 crown and 8 crown scaffold. For a 9 crownpattern and 7-9 mm outer diameter an angle exceeding 115 degrees, whileproducing a high radial stiffness, also exhibited fracture problems whendeployed and an unsatisfactory reduction in crush recoverability. Strutor crown angles found to produce acceptable results were between about105 and 95 degrees. For a 8 crown scaffold a smaller angle than 115degrees was preferred for the crown. For the 8 crown scaffold the angleis about less than 110 degrees. Generally speaking, the more crowns themore compliant becomes the scaffold radially and the higher the crownangle the less radially complaint becomes the scaffold.

Comparisons were made among mean radial strength (N/mm) and radialstiffness (N/mm) values after e-beam sterilization of a V2, V23 and V59constructed scaffold (having the properties summarized in FIGS. 6A-6B)with the Control stent, Igaki-Tamai stent, and Absolute stent (8.5 mmouter diameter, 36 mm length). Table 5 summarizes the findings.

TABLE 5 Radial strength and stiffness comparisons Radial strength Radialstiffness Stent/scaffold type (sterilized) (sterilized) Cordis ® 0.820.58 Igaki-Tamai 0.04 0.09 Absolute 8.5 ProLL 0.51 0.22 V2 (.008″ wallthickness) 0.32 0.54 V23 (.014″ wall thickness) 0.49 1.2 V23 (.008″ wallthickness) 0.4 0.59 V59 (.011″ wall thickness) 0.6 0.91

The V2, V23, and V59 had far superior strength and stiffness values overthe Igaki-Tamai stent. The V23 with 0.014″ had the highest radialstiffness. The V2, V23 and V59 strength and stiffness values werecomparable to the self-expanding stent.

Comparisons were also made between the pinching stiffness of scaffoldaccording to the disclosure. The values represent average values inunits of N/mm based on three samples. The stiffness values were computedfrom the measured force required to crush the scaffold to ½ or 50% ofits starting diameter, e.g., expanded or inflated diameter, using a flatplate test at 20 Deg Celsius.

TABLE 6 Pinching Stiffness average standard Stent/scaffold typestiffness deviation V2 (.008″ wall thickness; 36 mm length) 0.151 .005V23 (.008″ wall thickness; 38 mm length) 0.202 .004 V23 (.014″ wallthickness; 38 mm length) 0.394 .052 V59 (.011″ wall thickness; 36.5 mmlength) 0.537 .037

According to one aspect of the disclosure a crush-recoverable scaffoldhas a ratios of pinching stiffness to radial stiffness of between about4 to 1, 3 to 1, or more narrowly about 2 to 1; ratios of pinchingstiffness to wall thickness of between about 10 to 70, or more narrowly20 to 50, or still more narrowly between about 25 and 50; and ratios ofscaffold inflated diameter to pinching stiffness of between about 15 and60 or more narrowly between about 20 to 40.

According to another aspect of the disclosure a crush-recoverablescaffold has a desirable pinching stiffness to wall thickness ratio of0.6-1.8 N/mm².

According to another aspect of the disclosure a crush-recoverablescaffold has a desirable pinching stiffness to wall thickness*tubediameter ratio of 0.08-0.18 N/mm³.

Animal Studies

Two animal studies (“Study 1” and “Study 2”) were conducted for thescaffolds described in FIGS. 6A-6B. The scaffolds were implanted intothe iliofemoral artery of a healthy porcine model at 28, 90 and 180 daysto evaluate the effectiveness of the polymer scaffold.

Study 1: compares the V2 with a Cordis® S.M.A.R.T.® CONTROL® Iliacself-expanding stent having an 8 mm outer diameter and a 40 mm length(hereinafter the “control stent”). Among the features of the implantedV2 and control stent investigated in the study was the degree of, andrelated complications caused by a chronic outward force effect of theimplanted prostheses on the healthy artery at 28, 90 and 180 daysfollowing implantation.

Study 2: compares the V23-008 and V23-014 to determine the effect wallthickness has on scaffold performance, principally loss in lumen area,scaffold area and growth in neointimal thickness.

During the course of the studies the implanted prostheses was subject tovarious degrees of hip extension and flexion by the swine, which isbelieved to impose about 10-12% bending, and about 13-18% axialcompression of the implanted scaffold and control stent during a maximumhip and knee flexion.

FIG. 16 is a plot showing the mean minimal lumen diameter (MLD) of theartery for the control stent and scaffold as measured using opticalcoherence tomography (OCT). The measurements were taken after 28, 90 and180 days. After 28 days, the scaffold average MLD was about 3.6 mm (15samples) while the control stent mean MLD was about 4.7 mm (13 samples).After 90 days the scaffold mean MLD was about 4.4 mm (7 samples) and thecontrol stent mean MLD was about 3.6 mm (5 samples). After 180 days thescaffold mean MLD was about 4.4 mm (9 samples) and the control stentmean MLD was about 4.0 mm (7 samples). The variance in mean MLD after28, 90 and 180 days for the control stent was much larger than thevariance in mean MLD for the scaffold.

FIG. 17 shows the mean neointimal thickness (as measured by OCT) after28, 90 and 180 days. At 28 days the mean control stent neointimalthickness was about 0.4 mm (15 samples) while the mean scaffoldneointimal thickness was less than 0.2 mm (13 samples). At 90 days themean neointimal thickness for the control stent had increased to about0.43 (7 samples) whereas the mean neointimal thickness for the scaffoldhad decreased to about 0.1 mm (5 samples). At 180 days the controlstent's mean neointimal thickness had increased to 0.55 mm whereas thescaffold mean neointimal thickness had increased to about 0.19 mm. Atthe 28, 90 and 180 days the variance in neointimal thickness for thecontrol stent was much higher than for the scaffold. It should be notedthat the PLLA scaffold included a drug coating to reduce tissue growth,whereas the control stent did not have a similar drug coating on it.

FIG. 18 shows the amount of stenosis measured after 28, 90 and 180 daysusing OCT. The amount of stenosis was about 22% and 18% for the controlstent and scaffold, respectively, after 28 days. After 90 days theamount of stenosis for the control stent had increased to about 25%whereas the scaffold stenosis had decreased to about 5%. After 180 daysthe amount of stenosis for the control stent remained at about 25%whereas the scaffold stenosis had decreased to about 4%. The variance instenosis for the control stent was far greater than the scaffold after28, 90 and 180 days.

FIG. 19 shows angiography images of the implanted scaffold and controlstent, respectively, taken 180 days after implantation. The dark areasindicate the size of the lumen where the prostheses were implanted. Ascan be appreciated from these images, the lumen in the vicinity of thecontrol stent has narrowed considerably. It is believed the increase inneointimal thickness, reduced MLD and increased stenosis measured in thevicinity of the control stent, FIGS. 16, 17 and 18, respectively, aresymptoms of the chronic outward force imposed on the artery by theself-expanding control stent.

FIGS. 20 and 21 are plots at 28, 90 and 180 days using the QVAmeasurement technique (commonly used by physicians). FIG. 20 depicts themean and variance late loss (loss in lumen diameter after implantation)for the control stent and scaffold. FIG. 21 shows the mean and variancefor the MLD for the control stent and scaffold.

FIGS. 22 and 23 are plots at 28 and 90 days of the histomorphometricarea stenosis and neointimal thickening by histomorphometry,respectively, for the control stent and V2 scaffold. Both these plotsindicate a steady and less favorable increase in the area stenosis andneointimal growth whereas the area stenosis and neointimal growth forthe scaffold was about constant and less than the control stent.

FIG. 24 compares the minimum lumen and minimum scaffold areas for theV23 having a 0.008″ wall thickness (“V23/008”) with the V23 having a0.014″ wall thickness (“v23/014”) after 28 and 90 days. Both the minimumlumen area and minimum scaffold areas were higher for the V23 with a0.014″ wall thickness. FIG. 25 shows the lumen area loss after 28 and 90days. The V23 with 0.014″ wall thickness had less lumen area loss thanthe V23 with 0.008″ wall thickness. Also, there was less variance amongthe samples for the V23 with 0.014″ wall thickness. FIG. 26 shows themean neointimal thickness between the V23 with 0.008″ and 0.014″ wallthickness. There was less tissue growth on the luminal surface of thescaffold when the 0.014″ wall thickness was implanted.

The 30, 90 and 180 day animal studies comparing the control stent to theV2 scaffold indicate that the scaffold exhibits noticeably less problemsassociated with a chronic outward force as compared to the controlstent. The 30 and 90 day study comparing a 0.008″ and 0.014″ wallthickness scaffold indicate there is more likely a reduced loss in lumendiameter, scaffold diameter and less neointimal growth when a higherwall thickness is used for the scaffold.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

The invention claimed is:
 1. A method for making a medical device,comprising: (a) providing a polymeric tube; (b) cutting a pattern intothe tube by a laser, wherein the pattern includes: (i) a set of ringsincluding a proximal end ring, a distal end ring opposing the proximalend ring, and middle rings positioned between the end rings, whereineach ring is associated with its direct neighboring ring by links, andwherein at least one pair of neighboring middle rings can be delineated,via corresponding links there between, into closed cells comprising aW-V shaped zone; (ii) the rings include struts and crowns, the strutsfold towards and unfold away from each other at the crowns; (iii) atleast one of the links being a marker link, the marker link having afirst structure off a first side wall of the marker link for holding afirst marker and a second structure off a second, opposite side wall ofthe marker link for holding a second marker, wherein the first andsecond structures are not longitudinally off-set from one another off ofthe marker link; and (iv) wherein the polymeric tube is cut by the lasersuch that the set of rings and links are shaped to have a minimumcrimped diameter such that in the minimum crimped diameter, a pair ofrings, between which the marker link resides, do not make contact withthe first and second structures; and (c) placing the first and secondmarkers in the structures and forming a stent; and (d) crimping thestent to a crimped diameter on a section of a catheter deliveryassembly, such that the pair of rings, between which the marker linkresides, do not make contact with the first and second structures in thecrimped diameter, whereby a medical device comprising the stent andcatheter is produced.
 2. The method of claim 1, wherein the diameter ofthe tube is greater than an expanded diameter of the stent whenimplanted in a lumen.
 3. The method of claim 1, wherein the crimping actincludes a heating step of heating the stent to a temperature below theglass transition temperature of a polymer of the stent.
 4. The method ofclaim 1, wherein the minimum crimped diameter is less than the crimpeddiameter.
 5. The method of claim 1, wherein the stent is crimped on aballoon of the catheter assembly.
 6. The method of claim 1, wherein eachlink adjoins a pair of the neighboring rings at a crown of each ring,and wherein the minimum crimped diameter (MCD) is equal to the valuederived from equation 1 or equation 2:MCD=(ΣSwi+ΣCrj+ΣLwk)*(π)−1+2*WT  (equation 1)MCD=(ΣSwi+ΣCrj+ΣLwk)*(π)−1  (equation 2) such that ΣSwi (i=1 . . . n) isthe sum of n ring struts having width Swi; ΣCrj (j=1 . . . m) is the sumof m crown inner radii having radii Crj (times 2); ΣLwk (k=1 . . . p) isthe sum of p links having width Lwk; and WT is a ring wall thickness. 7.The method of claim 6, wherein each strut has an aspect ratio (AR) of0.8 to 1.4, AR being defined as ratio of width to thickness, and whereineach link has an AR of 0.4 to 0.9.
 8. The method of claim 1, whereineach link adjoins a pair of the neighboring rings at a crown of eachring, and wherein the minimum crimped diameter (MCD) is less than thevalue derived from equation 1 or equation 2:MCD=(ΣSwi+ΣCrj+ΣLwk)*(π)−1+2*WT  (equation 1)MCD=(ΣSwi+ΣCrj+ΣLwk)*(π)−1  (equation 2) such that ΣSwi (1=1 . . . n) isthe sum of n ring struts having width Swi; ΣCrj (j=1 . . . m) is the sumof m crown inner radii having radii Crj (times 2); ΣLwk (k=1 . . . p) isthe sum of p links having width Lwk; and WT is a ring wall thickness. 9.The method of claim 8, wherein each strut has an aspect ratio (AR) of0.8 to 1.4, AR being defined as ratio of width to thickness, and whereineach link has an AR of 0.4 to 0.9.
 10. The method of claim 1, whereinthe marker link is longer than the links which do not have a marker. 11.The method of claim 1, wherein a pre-crimped crown angle is greater thana deployment crown angle.
 12. The method of claim 1, wherein the firststructure and the second structure including the first and secondmarkers are circumferentially off-set from the marker link and spacedfrom the pair of rings associated with the marker link.
 13. The methodof claim 1, wherein at least one pair of the neighboring middle rings isadjoined by middle links, each middle link is associated with one crownof one ring and another crown of the neighboring ring, such that eachmiddle link and its corresponding crown for the one ring forms agenerally “Y” shaped structure and each middle link and itscorresponding crown for the neighboring ring forms a generally “W”shaped structure.
 14. The method of claim 1, wherein at least one of themiddle rings has undulated segments and a repeating pattern of “Y”shaped and “W” shaped constructions where the undulated segments meetthe links, and wherein the pattern further includes an undulated segmentthat is link-free between each “Y” and “W” shaped construction.
 15. Themethod of claim 1, wherein the minimum crimped diameter is an innerdiameter of the stent when the following step is performed: bending thestruts of the rings towards each other, wherein the struts bend at thecrowns, such that after bending, at least one of a pair of strutsadjoined by a crown is separated by a distance of about zero or the atleast one pair of struts is touching each other.
 16. The method of claim1, wherein the marker link and two strut segments of a ring associatedwith the marker link form a “Y” shaped segment.
 17. The method of claim1, wherein the set of rings comprises a first ring, a second ring, and athird ring, the second ring being positioned between the first and thirdrings, wherein the links residing between the first ring and the secondring are circumferentially off-set from the links residing between thesecond ring and the third ring.
 18. The method of claim 1, wherein atleast one of the struts has an aspect ratio (AR) of 0.8 to 1.4, andwherein at least one of the links has an aspect ratio of (AR) 0.4 to0.9, AR being defined as ratio of width to thickness.
 19. The method ofclaim 1, wherein each of the closed cells consists of 8 link-freecrowns.
 20. The method of claim 1, wherein the at least one pair ofneighboring middle rings forms only 3 W-V shaped closed cells.
 21. Themethod of claim 1, wherein the set of rings comprises a first ring, asecond ring, and a third ring, the second ring being positioned betweenthe first and third rings, and wherein the first and second rings,including the links there between, define a first set of W-V shapedclosed cells, wherein the second and third rings, including the linksthere between, define a second set of W-V shaped closed cells, andwherein the W-V shaped closed cells of the first set arecircumferentially off-set from the W-V shaped closed cells of the secondset.
 22. The method of claim 1, wherein at least some of the middlerings have a repeating pattern of “Y” shaped and “W” shaped crowns wherethe rings meet the links, and wherein the pattern further includes apattern of one and three link-free crowns between the “Y” and “W” shapedcrowns.
 23. The method of claim 1, wherein the links between a firstpair of rings are out of phase or circumferentially off-set from thelinks between a second pair of rings, the first pair of rings and thesecond pair of rings sharing a common interior ring; and wherein thelinks between the first pair of rings are out of phase orcircumferentially off-set from the links between a third pair of rings,the second pair of rings and the third pair of rings sharing a commoninterior ring.
 24. The method of claim 1, wherein the set of ringscomprises a first ring, a second ring next to the first ring, a thirdring next to the second ring, the second ring being in between the firstand third rings, and a fourth ring next to the third ring, the thirdring being in between the second and fourth rings, wherein the linksbetween the first ring and the second ring are circumferentially offsetfrom the links between the second ring and the third ring, wherein thelinks between the second ring and the third ring are circumferentiallyoffset from the links between the third ring and the fourth ring, andwherein the links between the first ring and the second ring arecircumferentially offset from the links between the third ring and thefourth ring.
 25. A method of making a medical device, comprising: (a)cutting a pattern into a tube by a laser, wherein the pattern includes:(i) a set of rings forming an open tubular body, the rings includingstruts that fold towards and unfold away from each other at crowns, (ii)a plurality of links, wherein each ring is associated with a neighboringring by links, and (iii) at least one of the links positioned between apair of rings is designated as a marker link, the marker link having afirst element off of a first side of the marker link for holding a firstmarker and a second element off of a second, opposite side of the markerlink for holding a second marker, (d) placing the first marker in thefirst element and the second marker in the second element and forming astent, wherein the first marker and second marker are positioned at adistance in a circumferential arrangement with respect to each othersuch that the first marker at least partially extends out from the firstside of the marker link and the second marker at least partially extendsout from the second side of the marker link, wherein the first andsecond elements are not longitudinally offset from each other, and (e)crimping the stent on a balloon of a catheter, such that in a crimpedconfiguration the pair of rings adjoined by the marker link do not makecontact with the first and second elements, and wherein the firstelement and second element including the first and second markers arearranged circumferentially off of the marker link and spaced from thepair of rings such that a crimped profile of the stent is the same asthe crimped profile of a same stent but without the first and secondelements.
 26. The method of claim 25, wherein the struts have an aspectratio (AR) of 0.8 to 1.4.
 27. The method of claim 25, wherein the ringsinclude end rings and middle rings such that at least one pair ofneighboring middle rings forms 3 W-V shaped closed cells.
 28. The methodof claim 25, wherein the set of rings comprises a first ring, a secondring, and a third ring, the second ring being positioned between thefirst and third rings, and wherein the first and second rings, includingthe links there between, define a first set of 3 W-V shaped closedcells, wherein the second and third rings, including the links therebetween, define a second set of 3 W-V shaped closed cells, and whereinthe W-V shaped closed cells of the first set are circumferentiallyoff-set from the W-V shaped closed cells of the second set.
 29. Themethod of claim 25, wherein the rings include end rings and middle ringswherein at least some of the middle rings have a repeating pattern of“Y” shaped and “W” shaped crowns where the rings meet the links, andwherein the pattern further includes a pattern of one and threelink-free crowns between the “Y” and “W” shaped crowns.
 30. The methodof claim 25, wherein the links between a first pair of rings are out ofphase or circumferentially off-set from the links between a second pairof rings, the first pair of rings and the second pair of rings sharing acommon interior ring; and wherein the links between the first pair ofrings are out of phase or circumferentially off-set from the linksbetween a third pair of rings, the second pair of rings and the thirdpair of rings sharing a common interior ring.
 31. The method of claim25, comprising a first ring, a second ring next to the first ring, athird ring next to the second ring, the second ring being in between thefirst and third rings, and a fourth ring next to the third ring, thethird ring being in between the second and fourth rings, wherein thelinks between the first ring and the second ring are circumferentiallyoffset from the links between the second ring and the third ring,wherein the links between the second ring and the third ring arecircumferentially offset from the links between the third ring and thefourth ring, and wherein the links between the first ring and the secondring are circumferentially offset from the links between the third ringand the fourth ring.